Hodder
Hodder
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1 Chemical signalling
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Guiding questions
• How do cells distinguish between the many signals that they receive?
• What interactions occur inside animal cells in response to chemical signals?
SYLLABUS CONTENT
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Transcription is (copying of the genetic code on to messenger RNA). These processes are examples of
covered in detail signal transduction.
in Chapter D1.2,
page 615.
Common mistake
◆ Signal transduction: Do not confuse ‘receptor protein’ with the term ‘receptor’. Receptors are specialized cells that
the conversion of an receive stimuli, and change (transduce) this signal into an electrical impulse (see Chapter C2.2).
impulse or stimulus from Receptor proteins are molecules that bind with ligands to convey messages into a cell, stimulating
one physical or chemical specific metabolic reactions.
form to another. In cell
biology, the process by
which a cell responds to receptor
Receptor protein
protein
an extracellular signal. for attachment signal
of specific chemical
◆ Second messenger: signalling molecule message
small intracellular ligand – a signal is then generated
(signalling molecule) that is transmitted inside the
generated or released cell
■ Figure C2.1.1 Outline of
inside a cell in response to cellular chemical signalling
an extracellular signal. (signal transduction)
◆ Effector protein: A chemical signalling pathway has one or more critical functions:
proteins that cause a
l Relay (‘pass on’) the signal onward and help spread it through the cell.
change inside a cell
during signalling. l Amplify the signal received (via a second messenger), making it stronger, so that a small
◆ Scaffold protein: number of ligands are enough to produce a large intracellular response. One ligand can activate
protein that binds two many signal transduction pathways to trigger many cell reactions simultaneously.
or more other proteins,
l Detect signals from more than one intracellular chemical signalling pathway and integrate them
and organizes binding
partners into a functional (two or more signals become one signal) before relaying a signal onward.
unit to enhance signalling l Distribute the signal to more than one effector protein, creating branches and resulting in a
efficiency. complex response (Figure C2.1.2).
Primary transduction is when the ‘message’ converts from being extracellular (outside the cell)
to intracellular (inside the cell). The scaffold protein holds some proteins close together, so the
reaction is faster.
The same signal molecule can trigger different cellular responses in two different cells in the body.
2 Suggest why Because different types of differentiated cells activate different sets of genes, different kinds of cells
chemical signalling have different collections of proteins.
in multicellular
organisms is more Concept: Interdependence
complicated than
in single-celled Chemical signalling relies on many different molecules to pass along the signal,
all needing to work together to control cell metabolism and keep the organism
organisms, such
working properly.
as yeast.
ATL C2.1A
Before learning more about cell signalling in this chapter, find out about this topic yourself by
watching the animation at this website: https://dnalc.cshl.edu/resources/3d/cellsignals.html
The animation shows how a fibroblast cell responds to external signals after an injury.
What knowledge of biology already covered in the course does this topic draw on? What aspects
of cell structure, cell membranes and proteins do you need to know about to understand how
cells respond to external chemical signals?
receptor protein
CYTOPLASM
scaffold
protein
relay
proteins
second messenger
integrator
protein anchoring
signal protein
molecules
bacteria modulator
cytoskeleton
protein
individual behaviours
messenger
high cell density protein
nuclear
envelope
RNA
target protein gene
transcription
DNA
target
NUCLEUS
group behaviours gene
■ Figure C2.1.3 Bacterial ■ Figure C2.1.2 Intracellular signalling proteins can relay, amplify, integrate and distribute the
quorum sensing incoming signal
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signalling molecule specific proteins inside the cell or in the bacterial cell membrane. When the autoinducer binds to the
produced and used by receptor, it activates or represses transcription of target genes, which often include those for
bacteria participating in
autoinducer synthesis.
quorum sensing.
When the bacterial population is low, diffusion reduces the concentration of the autoinducer in the
surroundings to a very low value. As the population increases, the concentration of the autoinducer
reaches a threshold, gene expression occurs and more autoinducer is synthesized. This forms a
positive feedback loop for autoinducer production.
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Positive feedback loops are covered later in this chapter, page 465, in fruit ripening in
Chapter C3.1, page 516, and in hormonal control of pregnancy in Chapter D3.1, page 722.
A well-known example of quorum sensing is shown by the bioluminescent marine bacterium Vibrio
fischeri, which produces the light-emitting enzyme luciferase when it reaches a critical cell population
density in the light organ of its host, the squid (Figure C2.1.4). It is of little benefit to V. fischeri to
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produce luciferase when it is on its own as a single cell. The bacteria do not emit light when they are
Mutualism as
an interspecific
outside of the host. The bioluminescence is very energy intensive and so the bacteria benefits from
relationship is covered being located within the animal where it can obtain nutrients. The squid also benefits from having
in Chapter C4.1, the bacteria: the light the bacteria emit attracts prey or can be used as camouflage. This interaction is
page 565. known as mutualism.
Going further
Cystic fibrosis is a genetic disorder. The most common symptoms are difficulty in
breathing and excessive mucus production. This is due to frequent lung infections often
involving large colonies of the bacterium Pseudomonas aeruginosa, which are resistant
to antibiotics because they produce enzymes and a biofilm when the cell density
exceeds a critical value detected by quorum sensing. A biofilm is a complex aggregation
of micro-organisms marked by the excretion of a protective and adhesive extracellular
matrix. The production of the biofilm provides the organism with protection against
■ Figure C2.1.4 Image
of the Hawaiian antibiotics and the enzymes damage the lung epithelium.
bobtail squid showing
bioluminescence produced
by Vibrio fischeri
Signalling chemicals in animals
In animals, many ligands may be classified as hormones, neurotransmitters, cytokines or calcium ions.
3 Outline the role
of quorum sensing ■ Hormones
in bacteria.
Hormones are secreted by endocrine glands and are carried through the circulatory system to act
4 Define the term on distant target cells. Hormones act over a longer time, work in cell metabolism and other functions
hormone. e.g. sexual reproduction. Hormones are discussed further later in this chapter on page 454.
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■ Neurotransmitters
Neurotransmitters carry signals between neurons or from neurons to other types of target cells
Neurotransmitters
are also covered (such as muscle cells). The release of neurotransmitters is caused by the arrival of an action potential
in Chapter C2.2, at the end of a neuron. Neurotransmitters are discussed further later in this chapter on page 455.
page 476; human
hormones are covered ◆ Hormone: extracellular signal molecule that is secreted and transported via the bloodstream (in
in Chapter D3.1, animals) or the sap (in plants) to target tissues where it causes a specific effect.
page 693 and D3.3, ◆ Neurotransmitter: chemical released at the presynaptic membrane of an axon when an action
page 760. potential arrives, which transmits the action potential across the synapse.
◆ Cytokines: small The cytokines form a family of relatively small, secreted proteins that control many aspects of
signalling molecules growth and differentiation of specific types of cells. Some cytokines, such as a-interferon, are
(usually a protein or produced and secreted by many types of cells after infection with viruses.
glycoprotein) made and
secreted by cells that act
on neighbouring cells to ■ Calcium ions
alter their behaviour. Most ligands are organic, but some metal ions are involved in cells signalling, especially calcium
ions (Ca2+ (aq)). Many ligands in animals, including neurotransmitters, growth factors and some
Top tip! hormones, induce responses in their target cells via signal transduction pathways that increase the
concentration of Ca2+ (aq) in the cytoplasm.
Note that some
neurotransmitters Increasing the cytoplasmic concentration of Ca2+ (aq) causes a number of responses in animal
can also act as cells, including muscle cell contraction, secretion of substances (for example, the neurotransmitter
hormones. For acetylcholine) and cell division.
example, epinephrine
Although cells always contain calcium ions, this ion can function as a second messenger because its
(adrenaline)
functions both as
concentration in the cytoplasm is normally much lower than the concentration outside the cell.
a neurotransmitter
and as a hormone
produced by the Chemical diversity of hormones
adrenal gland to signal
glycogen breakdown in
and neurotransmitters
muscle cells.
A wide range of extracellular molecules and ions can act as ligands for receptor proteins in cell
signalling pathways. They include metal ions, low molar mass compounds (for example, amino acids
and molecules derived from them), steroids, peptides and proteins.
■ Hormones
There are three main classes of hormone (Table C2.1.1): proteins (such as insulin), amines (also
known as amino acid derivatives, such as epinephrine) and steroids (such as cholesterol, which is
needed to synthesize oestradiol and testosterone). Hormones can be small, non-polar, hydrophobic
molecules that diffuse through the cell membrane to reach receptors in the nucleus or cytoplasm.
Examples are progesterone and testosterone, as well as thyroid hormones.
■ Table C2.1.1 Three main chemical classes of hormones
Hormone Protein/peptide
class hormones Steroid hormones Amine hormones
Example Insulin Oestradiol Epinephrine (adrenaline)
OH OH
H 2N
Phe
Val
H
Leu Ala
Tyr Glu
Asn
Gln CH3
HO N
Val
Leu His
Leu
Val
Leu
Gly Cys
CH3
His
Glu Cys
Arg S Ser
H 2N
Gly
S S
Gly Gly
COOH Asn S
Cys
Phe Tyr lle
HO
Cys
Phe Asn
Val Gln Cys Thr
Glu
Glu S
Tyr Ser
Leu S
Thr lle
Gln Cys
Pro Tyr Leu Ser
Lys
Thr
COOH
HO
Hormones can also be water-soluble molecules that bind to receptors on the plasma membrane.
They are either proteins like insulin and glucagon, or small, charged molecules like histamine
and epinephrine.
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of science: Neurotransmitters are a chemically diverse group of chemicals, including simple amines (for
Experiments example, dopamine), amino acids (for example, gamma-aminobutyric acid or GABA), polypeptides
(for example, endorphins) and acetylcholine (an amino acid derivative).
Evidence for the role
Although some neurons produce and release only one kind of neurotransmitter, most make
of nitric oxide (NO) in
causing the relaxation
two or more and may release one or more at any given time. The coexistence of more than one
of smooth muscle neurotransmitter in the synapse makes it possible for the cell to exert several influences at the
came from a set of same time.
experiments in which In the brain and other parts of the central nervous system, the gas nitric oxide (NO) functions as a
the neurotransmitter
neurotransmitter, or as an agent that influences neurotransmitters.
acetylcholine was
added to experimental
preparations of Concept: Interaction
the smooth muscle
cells that surround Neurotransmitters interact with the synapse to convey messages through the body.
blood vessels. The Several neurotransmitters in the same synapse allow a number of messages to be passed
direct application of on at the same time, and so allow varied responses to stimuli.
acetylcholine to these
cells caused them to
contract, the expected Going further
effect of acetylcholine
on these muscle cells.
Nitric oxide and cell signalling
However, addition
of acetylcholine to Nitric oxide (nitrogen monoxide, NO) gas molecules can rapidly diffuse across the
the lumen of small, plasma membrane into the cytoplasm of target cells and directly control the activity of
isolated blood vessels specific intracellular proteins. Nitric oxide is synthesized from the amino acid arginine
in culture medium and diffuses from its site of synthesis into nearby cells. The gas only acts locally because
caused the underlying it is quickly converted to a range of products by reacting with oxygen and water
smooth muscles to outside cells.
relax, not contract.
Later studies showed
Nitric oxide causes the smooth muscle in blood vessels to relax, causing the blood
that, in response to vessel to dilate (widen), increasing blood flow. Many nerve cells also use NO to signal
acetylcholine, the neighbouring cells.
endothelial cells that
line the lumen of blood
vessels were releasing
a substance (later
shown to be NO) that
Localized and distant effects
triggered muscle cell of signalling molecules
relaxation.
Cells in multicellular organisms usually communicate via ligands targeted for cells that may be either
adjacent (local chemical signalling) or not adjacent (long-distance chemical signalling).
◆ Synaptic signalling:
a type of cell–cell
communication that ■ Local chemical signalling
occurs across chemical Local signalling involves direct contact between cells. Neurons are separated by synapses. Synaptic
synapses in the
signalling occurs across chemical synapses and involves neurotransmitters such as acetylcholine
nervous system.
and norepinephrine. The gap between the presynaptic membrane and the postsynaptic membrane is
very small, between 20 and 40 nanometres (nm). Neurotransmitters therefore only have to transfer
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the signal over a small distance. While the immediate effect of the neurotransmitter is localized, the
Neurons and synapses
are covered in detail overall effect is widespread because the signal transmitted across the synapse enables an electrical
in Chapter C2.2, impulse to be established in the postsynaptic neuron and the message is transferred on through
page 467. the body.
channel: an ion channel membrane, acetylcholine binds with the neurotransmitter receptors (ligand-gated sodium channels)
that is stimulated to found on the postsynaptic membrane, causing the opening of ion channels. This results in the influx
open by the binding of a
small molecule such as a of sodium ions, Na+ (aq), which generates a new impulse in the postsynaptic neuron.
neurotransmitter. Other examples of local chemical signalling include gap junctions in animals and plasmodesmata in
◆ Ion channel: plants. In animals, cells may communicate between membrane-bound molecules on the cell surface
transmembrane protein
membrane (cell–cell recognition).
that forms a pore across
the bilayer through
which specific ions
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can diffuse down their Gap junctions are discussed in Chapter B2.1, page 243. Plasmodesmata are discussed in
concentration gradients. Chapter B3.2, page 306.
Top tip!
The same ligand can
Differences between transmembrane
bind to different and intracellular receptors
receptor proteins
causing different Receptor proteins can either be in the plasma membrane (transmembrane) or within the cytoplasm
responses (for example, (intracellular) (see Figure C2.1.5). The properties of a ligand determine the type of receptor that is
acetylcholine). On used. Some ligands are non-polar and therefore lipid-soluble, whereas others are charged and water-
the other hand,
soluble. Non-polar ligands can diffuse through the phospholipid bilayer and access receptor proteins
different ligands
within the cell. Polar ligands, such as peptide hormones (e.g. insulin and glucagon) are hydrophilic
binding to different
receptor proteins can and cannot pass through the phospholipid bilayer. These ligands must bind with receptor proteins
produce the same on the surface of the cell.
cellular response (for
a lipid-insoluble ligand b lipid-soluble ligand
example, glucagon and
epinephrine). target cell
target cell
receptor protein
receptor product protein synthesis
■ Figure C2.1.5 Lipid-
protein
insoluble ligands utilize
receptor proteins in activated enzyme
the plasma membrane, ligand–receptor
or other protein DNA
whereas lipid-soluble complex
ligands can diffuse
through the membrane mRNA
and access intracellular secondary messengers nucleus
protein receptors
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◆ Transmembrane
receptor protein: cell
It is incorrect to say that all receptor proteins are in the plasma membrane. The receptors on the
signalling receptor protein
that is in the membrane. surface of the cell respond to charged, polar ligands. Ligands that are lipid soluble, such as steroid
◆ Intracellular hormones, can pass through the phospholipid bilayer and so their receptors are inside the cell.
receptor protein: cell
signalling receptor protein Corresponding to the two classes of signal molecules there are, therefore, two classes of receptor
located inside the cell. proteins: transmembrane receptor proteins and intracellular receptor proteins.
hormone
of a gene may be switched on or switched off. If a gene
has been activated, new RNA is formed, leaves the
blood in
capillary nucleus and then directs the formation of new proteins
(most likely an enzyme) at ribosomes. The new protein
moves through
membrane by diffusion
or enzyme will bring about a structural or functional
change in the cell. Of course, if a gene is switched off by
steroid
receptor hormone action, some cell process will be interrupted
in cytoplasm or terminated.
gene structure/
activated function
to yield
mRNA
of cell
altered
Initiation of signal
transduction pathways
by receptors
For a cell to respond when it encounters a signal, the
activated
enzyme ligand must first be recognized by a specific receptor
molecule on the plasma membrane and then transmitted
to the cell’s interior before a cellular response can occur.
mRNA to
ribosomes in Cell signalling can be divided into three stages:
cytoplasm
1 Ligand–receptor interaction
2 Signal transduction
■ Figure C2.1.6 The mechanism of
action of a lipid-soluble hormone 3 Cellular response.
■ 1 Ligand–receptor interaction
5 Compare The ligand is complementary in shape to a binding site on the receptor and binds to it. There is
and contrast high specificity in the ligand–receptor binding. The binding of the ligand to the receptor activates
transmembrane the receptor.
and intracellular
receptor proteins.
■ 2 Signal transduction
The signal transduction pathway often requires a sequence of changes in a series of different
◆ Signal cascade: series molecules in a multistep pathway. These molecules in the pathway are often called relay molecules.
of linked reactions, often Signal transduction occurs via two main ways: protein phosphorylation in a phosphorylation signal
including phosphorylation
cascade and the release of second messengers, for example cyclic AMP (see Figures C2.1.2 and
and dephosphorylation,
that carries information C2.1.13). Such pathways also allow for signal amplification.
within a cell, often The activated receptor activates a relay molecule, which activates another relay molecule, and so
amplifying an initial signal.
on, until the molecule (usually a protein) that produces the final cellular response is activated.
◆ Phosphorylation
cascade: a sequence
Many of the relay molecules in signal transduction pathways are protein kinases and they often
of events where one act on other protein kinases in the pathway. Each activated protein kinase will initiate a sequential
protein kinase enzyme phosphorylation and activation of other kinases, resulting in a phosphorylation cascade.
phosphorylates another,
causing a sequence of Relay molecules are usually activated when they are phosphorylated, and deactivated when they
events that leads to the are dephosphorylated. The processes of phosphorylation and dephosphorylation act as a molecular
phosphorylation of many switch in the cell, turning metabolic activities on and off as required.
protein kinases. As the
signal is carried onwards
it is amplified and
■ 3 Cellular response
sometimes can spread to The signal transduction pathway leads to a specific cellular response, which is the regulation of one
other signalling pathways. or more cellular activities. The response may occur in the nucleus or the cytoplasm of a cell.
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programmed cell death l regulation of activity of protein (for example, the opening or closing of an ion channel in the
that allows cells that are plasma membrane changes the membrane permeability)
unneeded or unwanted
l regulation of protein synthesis by activating or deactivating specific gene expression by turning
to be eliminated from
an adult or developing genes on or off in the nucleus
organism. l regulation of the activity of an enzyme
l rearrangement of the cytoskeleton of the cell
l death of the cell (for example, apoptosis).
After the specific cellular response has occurred, the signal is terminated. The ability of a cell to
receive new ligands depends on the reversibility of the changes produced by previous signals.
Link
The role of sodium
Transmembrane receptors for neurotransmitters
ion channels is
discussed in Chapter
and changes to membrane potential
B2.1, page 239 and
The ligand-gated sodium ion channel (Figure C2.1.7) is composed of five transmembrane protein
their role in changing
membrane potential subunits. The protein subunits combine to form an aqueous pore across the lipid bilayer, which
is covered in C2.2, is lined by five transmembrane a-helices, one from each subunit. There are two acetylcholine
page 479. binding sites.
ACh Na+
nicotinic receptor
Going further
Curare
Curare (a plant
alkaloid) causes
muscle paralysis by
blocking excitatory
■ Figure C2.1.7 The open and closed conformations of the
acetylcholine acetylcholine receptor (ligand-gated sodium channels)
receptors at the
When acetylcholine released by a motor neuron binds to both acetylcholine binding sites, the
neuromuscular
channel undergoes a change in conformation (shape): the hydrophobic side chains move apart and
junction. It is used
by surgeons to relax the gate opens, allowing sodium ions to flow across the membrane down their electrochemical
muscles during and concentration gradient. This depolarizes the plasma membrane (Figure C2.2.4, page 471) and
an operation. changes the membrane potential (the voltage across the membrane), which leads to other changes
(see Chapter C2.2, page 467).
◆ GTP: guanosine
triphosphate with a role
Transmembrane receptors
in cell signalling. that activate G protein
◆ G protein: a
membrane-bound GTP is an energy-rich nucleotide like ATP, composed of ribose and three phosphate groups but with
GTP binding protein, guanine rather than adenine as the base. G proteins are membrane-bound GTP binding proteins,
usually activated by the
usually activated by the binding of a hormone or other ligand to a transmembrane receptor. They
binding of a hormone
or other ligand to a respond to extracellular signals from hormones and neurotransmitters, and trigger intracellular
transmembrane receptor. signalling cascades that regulate bodily functions.
G proteins are important in vision, as well as smell and taste. Their role is to couple the primary
stimuli (the light waves, odorants (molecules that cause smell) or flavourants (molecules that cause
receptor (GPCR): nerve impulse that flows from the sensory organ (such as the eye or nose) to the brain.
cell-surface receptor that
associates with a G protein. The G protein-coupled receptor (GPCR) is closely associated with a G protein, a protein that binds
to guanosine triphosphate or guanosine diphosphate (GDP).
G protein-coupled receptors have a common structure consisting of seven hydrophobic a-helices that
Top tip! span the plasma membrane (Figure C2.1.8). By forming hydrophobic interactions with the hydrophobic
GPCRs are only found core of the membrane lipid bilayer, the a-helices allow the receptor membrane to be embedded within
in eukaryotes, not the plasma membrane. Signal transduction from GPCRs is controlled by G proteins that bind mainly to
prokaryotes. There are the third and largest cytoplasmic loop in the polypeptide chain of the receptor.
nearly 1000 GPCRs and
many different signal NH2
molecules are specific
for different types of
GPCRs. These receptors
vary in their binding
sites for recognizing
signal molecules and
different G proteins
inside the cell. transmembrane α-helix
loop
COOH
Top tip!
Proteins fold in water
(a polar solvent) so
that hydrophobic
groups are buried
and polar groups are
exposed to the water
molecules. However, ■ Figure C2.1.8 A G protein-coupled receptor
proteins arrange The GPCR is inactive when not bound to a ligand. The G protein is inactive when bound to GDP.
themselves differently When the ligand binds to the extracellular side of GPCR, the receptor is activated, causing it to
in the bilayer of the
change its conformation. The change in conformation (shape) of the receptor when the ligand binds
plasma membrane
as it is a highly non-
activates a G protein, which in turn activates an effector protein that generates a second messenger,
polar environment; causing the G protein to exchange its bound GDP for GTP.
they expose their The G protein is activated and dissociates from the receptor, then binds to an enzyme or other
hydrophobic groups protein, activating it. Once activated, the enzyme triggers signal transduction leading to cellular
and hide polar groups
response. Once the signal molecule is absent, GTP is hydrolyzed back into GDP by the GTPase
in their core.
enzyme found in the G protein subunit. The G protein therefore dissociates from the enzyme and
returns to its inactive form. The signal is switched off (Figure C2.1.9).
◆ GTPase: an enzyme
that hydrolyzes GTP into receptor membrane-bound ions ion channel
GDP and Pi. ligand effector protein
■ Figure C2.1.9
second
Mechanism of action GDP GTP messengers
of G protein-coupled GDP GTP GTP
receptors; GDP is
G-protein activated G-protein
dislodged when GTP G-protein subunits or second
interacts with G protein messengers modulate ion channels
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Physical molecular modelling
Make a paper model of a G protein-coupled receptor using this site:
https://pdb101.rcsb.org/learn/paper-models/g-protein-coupled-receptor-gpcr
The site provides a template PDF to download and print. How does the structure of the
protein enable it to carry out its function? Use your model to explain to someone else in
your class how the G protein-coupled receptor functions.
adenylate cyclase: activated by the G protein, can catalyse the conversion of ATP to many cyclic AMP (cAMP)
enzyme that catalyses molecules. The concentration in the cytoplasm of the cAMP is increased very rapidly, amplifying
the formation of cAMP
from ATP.
the signal in the cytoplasm. It does not last for long because another enzyme, called
phosphodiesterase, converts the cAMP to AMP, resulting in signal termination.
◆ Phosphodiesterase:
enzyme that catalyses The hormone activates a GPCR, which turns on a G protein (GS) that activates adenylyl cyclase
the breaking of a to boost the production of cAMP. The increase in cAMP activates PKA (cAMP-dependent protein
phosphodiester bond in
an oligonucleotide.
kinase), which phosphorylates and activates an enzyme called phosphorylase kinase, which activates
◆ Kinase: enzyme that
glycogen phosphorylase, the enzyme that breaks down glycogen.
catalyses the transfer of In skeletal muscle, epinephrine increases the concentration of intracellular cyclic AMP, causing the
a phosphate group from breakdown of glycogen by activating PKA, which leads to both the activation of an enzyme that
ATP to a specific amino
acid side chain on a target promotes glycogen breakdown and the inhibition of the enzyme that catalyses glycogen synthesis
protein. (Figure C2.1.11).
◆ Phosphorylase: By stimulating glycogen breakdown and inhibiting its synthesis, the increase in cyclic AMP
enzyme that breaks maximizes the amount of glucose available as a respiratory substrate for muscular activity.
down glucose-based
polysaccharides Epinephrine also acts on adipose cells, stimulating the breakdown of fat to fatty acids, which can
(e.g. glycogen) to glucose also be used to generate ATP by respiration.
1-phosphate. The relay molecules are activated kinases and phosphorylases. These proteins catalyse specific types
inactive cAMP
of reactions:
kinase l Kinases are enzymes that transfer a phosphate group from ATP to an acceptor.
enzyme
l Phosphorylases are enzymes that break down glucose-based polysaccharides (e.g. glycogen) to
active kinase enzyme
inactive glucose 1-phosphate.
phosphorylase
enzyme
The critical role of the second and third stages of signal transduction is the amplification of the
active phosphorylase enzyme hormone signal (see page 458). So, from one activated receptor molecule, 10 000 (104) molecules
of cAMP are formed. As a result of the presence of cAMP in the cytoplasm, approximately 106
glycogen molecules of active phosphorylase enzyme will be formed, and these will then trigger the formation
glucose 1-phosphate of perhaps 108 molecules of glucose 1-phosphate.
■ Figure C2.1.11
Nature of science: Science as a shared endeavour
I B L E AR N
Cascade of reaction HE
ER
T
PROFILE
triggered by the
binding of epinephrine
to a target cell
The IUPAC chemical name of epinephrine is (R)-1-(3,4-dihydroxyphenyl)-2-methylaminoethanol. In
Japan and the USA, the substance is known as epinephrine, but in most other countries it is known
as adrenaline. Adrenaline is marketed in Britain as ‘Epipen’ for intramuscular injection and as Eppy
or Simplene for eyedrops.
George Oliver, a medical doctor, and Edward Schäfer, a professor of physiology, both in the UK,
showed that the adrenal glands contained a substance with strong pharmacological effects. It was
named ‘epinephrine’ by John Abel in the USA in 1897.
In 1901, after visiting Abel, Jokichi Takamine, a Japanese chemist, prepared a pure extract of the
active principle from the adrenal gland and patented it. A company marketed his extract and,
because they used the proprietary name adrenaline, epinephrine became the generic name in
America and Japan.
Top tip! There are arguments to prefer adrenaline over epinephrine. The gland is the adrenal gland, not the
epinephric gland. However, the gland is above (‘epi’) the kidneys (which contain structures called
Because these nephrons) hence ‘epinephrine’. Unusually, these two terms persist in common use in different
reactions do not parts of the world. Naming conventions show international cooperation in science for mutual
involve changes in benefit. In the case of adrenaline/epinephrine, conventions developed by one set of scientists have
gene transcription or not been adopted by others, although overall the two names are widely understood, as is their
new protein synthesis, interchangeability. The IUPAC chemical name is internationally understood, although it would be
they occur rapidly. unrealistic to use this in everyday discussions of this hormone!
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The story of (R)-1-(3,4-dihydroxyphenyl)-2-methylaminoethanol is interesting in that it shows
how reliant the development of biological knowledge is on the community of biologists. The
interactions and sharing of knowledge between Oliver, Schäfer, Abel and Takamine all resulted in
new knowledge and development of the chemical, although under various names. This emphasizes
how new knowledge, and the language used to express the knowledge, sometimes takes time
to formalize. One important function of the IUPAC is to create a single, authoritative source of
knowledge in chemistry for the various scientific communities that use it.
Key:
+ ligands
ligands
tyrosine kinase domain
P phosphorylation
P P
OFF P P
P P
◆ Dimer: a molecule
ON
composed of two
structurally similar ■ Figure C2.1.12 Activation of an RTK stimulates the assembly of an intracellular signalling complex
subunits.
An RTK is a single polypeptide chain with a single transmembrane a-helix, an extracellular ligand
◆ Dimerisation: the
formation of a dimer binding site and an intracellular tail that functions as tyrosine kinase and contains many tyrosine
(from two monomers). amino acid residues.
◆ Autophos- Before a ligand binds, the receptors exist as individual RTK monomers. The binding of a ligand to the
phorylation: the
phosphorylation of a
extracellular binding sites of RTKs causes two RTK proteins to associate together in the membrane,
kinase by itself. forming a dimer (Figure C2.1.12). Dimerisation brings a suitable substrate up to the kinase active
◆ Relay protein: site in the intracellular tails of RTK. Tyrosine kinase adds a phosphate group from an ATP molecule
a protein that passes the to the tyrosine residues on the tail of the other RTK protein by autophosphorylation.
signal to the next member
of the signalling pathway. The activated RTK will trigger the assembly of specific relay proteins on the receptor tails, activating
◆ Gluconeogenesis: them. Each activated protein triggers a signal transduction pathway, leading to a cellular response.
set of enzyme-catalysed
reactions by which ■ Insulin signalling
glucose is synthesized
Insulin functions as an extracellular messenger molecule (hormone), informing cells that glucose
from small organic
molecules such as levels are high. Cells that express insulin receptors on their surface, such as cells in the liver, respond
pyruvate, lactate or to this message by increasing glucose uptake, increasing glycogen and triglyceride synthesis, and/or
amino acids. decreasing gluconeogenesis. The ligand (insulin) binds to an insulin receptor, an RTK.
enzymatic formation or cause vesicles embedded with glucose transporter proteins to move to the cell surface membrane.
synthesis of glycogen. The vesicles fuse with the plasma membrane, inserting the transporter proteins into the cell surface
membrane, which results in the increase in uptake of glucose into muscle cells.
Many glycogen synthase molecules are activated, which will catalyse the synthesis of glycogen from
glucose (glycogenesis). Hence the binding of a single insulin molecule to a receptor will lead to the
synthesis of large amounts of glycogen.
The signal is terminated when insulin is released from receptors, the tyrosine residues are
dephosphorylated by phosphatases and the two halves of the dimer separate. Protein phosphatases
inactivate protein kinases by dephosphorylation.
Figure C2.1.13 shows the effect of insulin on cells. The numbers in the figure
correspond to the following events:
1 Insulin activates RTK receptors.
2 Relay proteins are activated, which travel to vesicles within the cell.
3 These vesicles contain glucose transporter proteins (channel proteins known
as GLUT4 (glucose transporter type 4).
4 The GLUT4 vesicles fuse with the plasma membrane.
5 The GLUT4 proteins become incorporated in the membrane, where they
transport glucose into the cell.
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a fluid-filled spherical
sac that contains and and progesterone on target cells
nourishes an immature
egg, or oocyte. In the ovary, each ovum (egg) is surrounded by a protective structure called the ovarian follicle,
◆ Oestradiol: a steroid which nourishes the ovum. The follicle also secretes the steroid hormones oestradiol and
hormone; a sex hormone
progesterone. Oestradiol is synthesized mainly in the ovary, but also in the placenta, testis and
of female mammals.
possibly the adrenal cortex. Oestradiol controls the development and maintenance of female
◆ Progesterone:
hormone released by sex characteristics.
the corpus luteum that The production of oestradiol in women’s ovaries is controlled by hormones released from both the
stimulates the uterus to
prepare for pregnancy.
hypothalamus in the base of the brain and the pituitary. The hypothalamus releases a hormone
called gonadotropin-releasing hormone. This hormone then acts on the pituitary gland to cause
the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are involved
in the menstrual cycle. The target cells, as well as being located in the pituitary, are also located in
Link the lining of the uterus, breasts and bone marrow. The interaction between the hormone and these
Control of the tissues leads to the development of female secondary sexual characteristics in puberty.
developmental
changes at puberty Once a month, one egg is released from a follicle in a process known as ovulation. After ovulation,
is covered in Chapter the follicle becomes a structure known as the corpus luteum. Progesterone is produced primarily
D3.1, page 709.
by the corpus luteum but also by the placenta and prepares the inner lining of the uterus
(endometrium) for implantation of a fertilized ovum. If implantation fails, the corpus luteum
Link
degenerates and progesterone production stops. If implantation occurs, the corpus luteum continues
The menstrual cycle,
ovulation and changes to secrete progesterone, under the influence of LH and prolactin, for several months of pregnancy,
during the ovarian after which the placenta takes over this function. During pregnancy, progesterone maintains the
and uterine cycles endometrium of the uterus and prevents further release of ova from the ovary.
and their hormonal
regulation are covered
7 State the type of chemical signalling shown by the secretion of hormones from the
in detail in Chapter
D3.1, page 698. pituitary gland.
+ −
■ Figure C2.1.14 Positive and negative feedback within an intracellular chemical signalling pathway
Top tip!
Positive feedback can generate all-or-none, switch-like responses, but negative feedback can
generate responses that oscillate on and off. More typically they act after some time delay to shut
down the pathway once it has produced its effects.
LINKING QUESTIONS
1 What patterns exist in communication in biological systems?
2 In what ways is negative feedback evident at all levels of organization?
Guiding questions
• How are electrical signals generated and moved within neurons?
• How can neurons interact with other cells?
SYLLABUS CONTENT
◆ Motor neuron: nerve cell that carries impulses away from the
central nervous system to an effector (e.g. muscle, gland).
◆ Axon: fibre carrying impulses away from the cell body of
a neuron.
◆ Sensory neuron: nerve cell carrying impulses from a sense
organ or receptor to the central nervous system.
◆ Receptor: a cell specialized to respond to stimulation by the
production of an action potential (impulse).
Specialized nerve cells (neurons) are organized into the central
nervous system and peripheral nerves linking sense organs, ◆ Dendron: fibre carrying impulses towards the cell body of
muscles and glands with the brain or spinal cord. a neuron.
◆ Relay neuron: a specialized cell in the central nervous system
■ Figure C2.2.1 The organization of the
which relays an electrical impulse from a sensory neuron to a
mammalian nervous system
motor neuron.
◆ Schwann cells: cells A neuron is surrounded by many supporting cells. One type of supporting cell are Schwann cells
of the peripheral nervous (Figure C2.2.2), which wrap around the axons of motor neurons, forming a structure called a myelin
system that wrap around sheath. Myelin consists largely of lipid and has high electrical resistance. The myelin sheath also
the axons of motor and
contains protein (between 15% and 25% of dry mass). Frequent gaps occur along a myelin sheath,
sensory neurons to form
the myelin sheath. between the individual Schwann cells. The gaps are called nodes of Ranvier.
◆ Myelin sheath: an
insulating sheath around
the axons of nerve fibres
Common mistake
formed by Schwann cells.
Do not confuse effectors and receptors. Receptors detect stimuli and effectors respond to them.
◆ Nodes of Ranvier:
Sensory neurons pass impulses from receptors to the CNS. Motor neurons stimulate effectors
gap in the myelin sheath
around a myelinated (muscles or glands) and affect movement.
nerve fibre.
axon
direction
of
myelin sheath
impulse cell body
Top tip!
Energy from ATP drives the pumping of sodium and potassium ions in opposite directions across the
plasma membrane of neurons. ATP is derived from aerobic respiration. Even when ‘doing nothing’,
the nervous system needs to use ATP to maintain the resting potential.
motor neuron
part of axon
(cut open)
resting potential
+ + + + + + + + + + + + + + +
+ +
– – – – – – – – – – – – – – –
+ – – +
– –
– – – – – – – – – – – – – – + – – +
2 Outline how a –
+ +
+ + + + + + + + + + + + + + +
resting potential
is generated.
■ Figure C2.2.3 The resting potential of an axon
action potential
+ + + + + – + + + + + – + + + +
– – – – – + – – – – – – + – – – –
motor
end plates
dendrites cell body nucleus axon myelin sheath node of Ranvier
unmyelinated axon
action potential
direction of impulse
+ + + ++ + + + – – – + + + + + + + +
– – – –– – – – + + + – – – – – – – –
+ + + ++ + + + – – – + + + + + + + +
Tool 2: Technology
HE
I B L E AR N
PROFILE
Concluding
Analyse the data you found for Table C2.2.1.
Compare the speed of transmission in animals that have myelination and those that do
not. Which have the faster conduction speeds overall? Why is this?
Now compare the animals that have unmyelinated axons, such as the giant axons of
squid and those animals with smaller, unmyelinated nerve fibres.
What conclusions can you reach about the effect of axon diameter size and myelination
Top tip! on conduction velocity? What explanation can you develop for these observations?
Some invertebrates,
such as the squid and
You should have carried out the activities on this page and the previous page and drawn your own
the earthworm, have
conclusions. You can now read on!
giant fibres, which
allow fast transmission In the Tools and Inquiry activities, you should have found that myelinated fibres have a faster
of action potentials conduction speed compared to unmyelinated fibres. This is discussed further below. In addition, an
(although not as fast as unmyelinated fibre with a large diameter transmits an action potential much faster than a narrow
in myelinated fibres).
fibre does. This is because the speed of transmission depends on resistance offered by the axoplasm
(cytoplasm inside the axon). The narrower the fibre, the greater its resistance, and the lower the
speed of conduction of the action potential. Incidentally, the original investigations of the nature of
the action potential by physiologists were carried out on giant fibres.
Nervous systems have therefore evolved two contrasting
mechanisms for increasing the conduction speed of the
electrical impulse. One is through developing giant axons:
80 using axons several times larger in diameter than is normal
conduction velocity (m/sec)
myelinated axons for other large axons. Giant axons are found in squid (Loligo
(cat)
60 sp., a type of aquatic mollusc). The other mechanism is by
using the myelin sheath, where axons are wrapped by cells
that have high amount of lipid in their plasma membrane
40 (Schwann cells). Each mechanism, on its own or in
combination with the other, is used in the nervous systems
unmyelinated axons
20 (squid) of many different groups of animals, both vertebrate
and invertebrate.
The presence of a myelin sheath speeds up transmission
0
0 1 2 3 4 5 6 7 8 9 10 11 12
of the action potential because it is only at the nodes of
diameter of myelinated axons (µm) Ranvier that the axon membrane is exposed and the action
potential can ‘jump’ from node to node. The electrical
0 200 400 600 800 resistance of the myelin sheath prevents reversal of the axon
diameter of unmyelinated axons (µm) polarity at the nodes of Ranvier. By contrast, the step-by-
■ Figure C2.2.5 Conduction velocities of myelinated step travel of the action potential along the entire surface
and unmyelinated axons as functions of axon diameter.
Myelinated axons have faster conduction velocities than of the fibres in unmyelinated dendrons and axons is a
unmyelinated axons that are 100 times greater in diameter relatively slow process (Figure C2.2.4).
Action potential propagation (or conduction) velocity is directly correlated with the axon diameter
(Figure C2.2.5 and Table C2.2.2). The larger the axon diameter, the higher the action potential
propagation velocity will be, which means signals can travel more quickly. This is because there
is less resistance facing the ion flow. In addition, myelination, which leads to the action potential
jumping between nodes along axons, greatly increases the action potential propagation velocity.
Despite having much smaller diameters, myelinated axons achieve much higher action potential
propagation velocities than unmyelinated axons. Figure C2.2.5 shows the correlation between axon
diameter and conduction speed in both myelinated and unmyelinated axons.
where m is the slope of the line and b is the value on the y-axis where the line crosses; y is the
dependent variable and x is the independent variable.
Top tip!
Correlations can either be negative or positive. Correlation coefficients can be applied as a
mathematical tool to determine the strength of these correlations. The coefficient of determination
(R2) is one such tool that can be used to evaluate the degree to which variation in the independent
variable may explain the variation in the dependent variable.
R2 indicates the extent that the dependent variable can be predicted. If R2 is 0.20, it means that 20%
of the variance in the y variable is predicted from the x variable. If the value is 0.50, it means that
50% of the variance in the y variable is predicted from the x variable, and so on.
Tool 3: Mathematics
Applying the coefficient of determination (R2) to evaluate the fit of a trend line
Steps to find the coefficient of determination: 1 Highlight the data and select ‘Insert – Chart – Scatter’.
1 Find R, the Pearson correlation coefficient. 2 Select chart area and select ‘+’ to add axes labels –
2 Square R. add labels for each axis.
3 Change the above value to a percentage. 3 Click on any data point. Right click and select ‘Add
trendline’. Select ‘linear’ trendline.
The formula for the Pearson correlation coefficient is:
4 Under ‘Trendline options’, select ‘Display R-squared
n (∑xy) – (∑x)(∑y)
R=n value on chart’. The R2 will appear above
[n∑x – (∑x)2] [n∑y2 – (∑y)2]
2
the trendline.
Where:
The graph should appear as follows:
n = total number of observations
100
∑ x = total of the first variable value 90 R2 = 0.9875
80
∑ y = total of the second variable value
70
conduction (m s−1)
axon of
presynaptic
direction of
neuron
transmission
myelin sheath
endoplasmic
reticulum
Golgi electron micrograph of a synapse (×80 000)
apparatus synaptic knob
mitochondrion
vesicles containing
transmitter substance
presynaptic
synaptic membrane
cleft
postsynaptic
membrane
synaptic knob
of postsynaptic
neuron
◆ Neurotransmitter: The practical effect of the synaptic cleft is that an action potential can only cross it via specific
chemical released at the chemicals, known as neurotransmitter substances. Neurotransmitter substances are all relatively
presynaptic membrane of small molecules that diffuse quickly. They are produced in the Golgi apparatus in the synaptic knob
an axon on arrival of an
and are held in tiny vesicles before release. The way that neurotransmitters cross the synapse, from
action potential, which
transmits the action presynaptic membrane to postsynaptic membrane, ensures that a signal can only pass in one
potential across the direction across a typical synapse.
synapse.
Top tip!
Link
The structure and Acetylcholine exists in many types of synapse, including neuromuscular junctions.
function of motor
units in skeletal muscle Neuromuscular junctions are a specialized synapse between a motor neuron nerve ending and its
are covered in Chapter muscle fibre. They are responsible for converting electrical impulses generated by the motor neuron
B3.3, page 332.
into electrical activity in the muscle fibres. When an action potential arrives at the neuromuscular
junction, vesicles of acetylcholine are released and the transmitter molecules bind to receptors on the
5 Define the term
sarcoplasm (this is the plasma membrane of the muscle fibre). This triggers the release of calcium
neurotransmitter.
ions from the sarcoplasmic reticulum, which leads to muscle contraction (see page 327).
Common mistake
Do not forget to refer to to the removal of the neurotransmitter by an enzyme such as
cholinesterase when discussing how the synapse functions.
1 Impulse arrives
at synapse and 5 Re-formation of
triggers Ca2+ transmitter
ion entry. substance vesicles.
Ca2+
ions
4 Enzymic
inactivation of
transmitter.
2 Transmitter
substance
released, 3 Transmitter substance binds, triggering
diffuses to entry of Na+ ions, and action potential
receptors of in postsynaptic membrane.
postsynaptic
membrane.
transmitter substance cycle
re-formation
using energy
from ATP
1 permeability 5
to Ca2+
increases
re-entry
release
2 diffusion
diffusion enzymic
3
inactivation 4
binding
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◆ Depolarization:
a temporary and local during action potentials
reversal of the resting
potential difference An action potential is triggered by a stimulus that is received at a receptor cell or sensory nerve
of the membrane that ending. The energy of the stimulus causes a temporary and local reversal of the resting potential.
occurs when an impulse
The result is that the membrane is briefly depolarized. Following the action potential there is a
is transmitted along
the axon. return of polarity towards the resting potential – this is known as repolarization. When the resting
◆ Repolarization: potential has been restored, the axon is said to be repolarized.
return of polarity towards This change in potential across the membrane occurs because of ion channels in the membrane.
the resting potential
following depolarization.
These special channels are globular proteins that span the membrane. They have a central pore with
◆ Voltage-gated
a gate that can open and close. One type of channel is permeable to sodium ions and another to
channels: a type of potassium ions. During a resting potential these channels are all closed.
transmembrane protein The transfer of energy of the stimulus first opens the gates of the sodium channels in the plasma
that forms ion channels
activated by changes in membrane and sodium ions diffuse in, down their electrochemical gradient. Because the channels
the electrical membrane open due to changes to the potential difference (voltage) across the membrane, they are called
potential of a neuron. voltage-gated channels.
Link
Top tip!
Voltage-gated
channels are also Sodium ions are predominantly found outside the membrane and, when they enter the neuron, their
covered in Chapter positive charges increase in that part of the membrane inside the cell. Positively charged potassium
B2.1, page 240. ions are predominantly found inside the cell and, when they flood out, the inner side of the membrane
becomes more negatively charged.
depolarization
Ion movements during the action
due to Na+ entry
potential:
action refractory 1 During the resting potential the ion channels for
+50 potential period Na+ ions and K+ ions are both closed.
+40 2 Na+ channels open and Na+ ions rush in
change in potential difference in 4
+30 (by diffusion).
plasma membrane of neuron
membrane potential/mV
ATL C2.2C
Explanations in biology are often complex, such as how the action potential works. By making
links to existing biological knowledge, and subdividing complicated processes into smaller
‘chunks’, difficult biological ideas can be better understood and remembered.
The following video shows you how the action potential can be broken down into a series of
processes that draw on your existing knowledge of biology to explain key ideas in a coherent and
easy-to-follow way: www.youtube.com/watch?v=7EyhsOewnH4
Create a poster showing the events of the action potential, summarizing key processes in a simple
and visually memorable way. Keep this for future reference – it will be useful when you come to
revise this topic!
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During the resting potential, sodium ions are predominantly outside the neuron and potassium ions
mainly inside. Following depolarization (sodium influx) and repolarization (potassium efflux), this
ionic distribution is largely reversed. Before a neuron can fire again, the resting potential must be
restored via the sodium–potassium pump. For a brief period, therefore, following the passage of an
◆ Refractory period: action potential, the neuron fibre is no longer excitable. This is the refractory period, and it lasts
the period immediately only 5–10 milliseconds in total. The neuron fibre is not excitable during the refractory period
following stimulation because there is a large excess of sodium ions inside the fibre and further influx is impossible.
when a nerve or muscle
is unresponsive to further Subsequently, as the resting potential is progressively restored, it becomes increasingly possible for
stimulation. During this an action potential to be generated again. Because of the refractory period, the maximum frequency
period the voltage-gated of impulses is between 500 and 1000 per second.
sodium channels are closed
and will not respond to Because areas of the membrane that have recently depolarized will not depolarize again due to the
changes in voltage. refractory period, the action potential only travels in one direction.
no action potential
■ Figure C2.2.10 Weak and strong stimuli and the threshold value
■ Figure C2.2.11 Diffusion of sodium ions both inside and from outside an axon can cause the
threshold potential to be reached
As sodium ions enter the axon, causing depolarization, they flow to adjacent areas, which causes
these areas to become less negative. This leads to further depolarizing and the opening of voltage-
gated sodium channels. This causes the action potential to move along the axon. The areas of the
membrane that have recently depolarized will not depolarize again because of the refractory period,
which means that the action potential will only travel in one direction.
Action potentials are therefore propagated along the axons of neurons via local currents. Local
currents induce depolarization of the adjacent axonal membrane and, where this reaches a threshold,
further action potentials are generated.
(II)
be measured.
difference/mV
(III)
(I)
Figure C2.2.12 shows two oscilloscope traces of specific events in an
axon of a postsynaptic neuron.
(IV)
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◆ Saltatory The presence of a myelin sheath affects the speed of transmission of the action potential. Only at
conduction: how an the junctions in the sheath, at the nodes of Ranvier, is the axon membrane exposed. Ion pumps and
electrical impulse jumps channels are grouped at nodes of Ranvier. Elsewhere along the fibre, the electrical resistance of the
from node to node
along a myelinated axon, myelin sheath prevents depolarization of the membrane. The action potentials actually ‘jump’ from
speeding the arrival of the node to node. This is called saltatory conduction, meaning ‘to leap’ (Figure C2.2.13). This greatly
impulse (in comparison speeds up the rate of transmission.
with the slower
continuous progression By contrast, unmyelinated dendrons and axons are common in invertebrate animals. Here, step-by-
of depolarization step depolarization occurs as the action potential flows along the entire surface of the fibres. This is a
spreading down an relatively slow process compared with saltatory conduction.
unmyelinated axon).
direction of impulse
12 Explain why
myelinated fibres
conduct impulses
faster than
Na+ out axon Na+ in myelin K+ out
unmyelinated fibres node of Ranvier sheath
of the same size.
■ Figure C2.2.13 Saltatory conduction between small gaps in the myelin sheath
■ Neonicotinoids
Neonicotinoids are a type of pesticide that completely block synaptic transmission at the cholinergic
synapses (synapses that have receptors that are activated when they bind to acetylcholine) of insects.
They are similar in structure to nicotine.
l Neonicotinoids bind to acetylcholine receptors in synapses in the CNS of insects, blocking the
binding of acetylcholine, inhibiting synaptic transmission.
l They cannot be broken down by acetylcholinesterase and so their effects are irreversible.
l There are issues about their impact on the wider insect community – concerns have been raised
about their effects on honeybees.
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body of a postsynaptic neuron
synapses
cell body of
postsynaptic neuron
axon
myelin sheath
(protective/insulatory)
incoming impulses
outgoing impulses
Key
excitatory synapse
inhibitory synapse 7 mm
◆ Summation: the
process that determines
Summation
whether or not an In general, at a synapse an action potential will only be generated in the postsynaptic neuron if the
action potential will
be generated by the combined effects of the excitatory action potentials and inhibitory action potentials exceed the
combined effects of threshold level. As we have already seen, the action potential is an all-or-nothing event: if the
excitatory and inhibitory threshold potential is not reached through the additive effect of postsynaptic potentials –
signals, both from
summation – then the action potential will not be generated. In excitatory synapses, the incoming
multiple simultaneous
inputs (spatial summation) action potential excites the postsynaptic membrane and generates an action potential that is
and from repeated inputs transmitted along the postsynaptic neuron. Inhibitory synapses make it more difficult for the
(temporal summation). postsynaptic cell to generate a nerve impulse in response to excitation by other (excitatory) synapses
present on the same postsynaptic cell. Several impulses may arrive at the synapse in quick
succession from a single axon, causing an action potential in the postsynaptic neuron
(temporal summation).
Alternatively, impulses from several different axons may contribute to the total (spatial summation).
Summation contributes to the decision-making processes of the brain, for example. In each case, the
additive effect of the different postsynaptic potentials needs to be sufficient to reach the threshold
potential of the axon in order to stimulate an action potential.
There are complex interactions between the activities of excitatory and inhibitory presynaptic
neurons at the synapses, operating with unimaginably numerous connections between the vast
numbers of neurons present (Figure C2.2.15).
+ +
+
+ positively charged ions
+
Capsaicin is a chemical compound found in chilli peppers. Another in this group of channel
proteins, TRPV1, is a single protein molecule that can respond to both heat and capsaicin. How
did a thermosensor like TRPV1 become sensitive to a plant product like capsaicin? One answer
is that TRPV1 evolved in some animals as temperature sensors and that certain plants then
developed compounds that would activate these sensors in order to deter consumption of the plants
by predators. Plants that produced capsaicin would therefore have a survival and reproductive
advantage, and become more widespread in the population of that species. Plant evolution therefore
drove the dual function of the sensors.
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When mammals eat chilli peppers, they tend to destroy the seeds with their molars.
Unlike mammals, birds have beaks and so pass most of the seeds through their digestive
system undamaged. When they defecate, they spread viable chilli pepper seeds to new
locations. Mammals respond to the capsaicin in chillies and detect the chemical as pain –
this deters them from eating chillies. Why do birds continue to eat chillies?
Birdwatchers often add chilli pepper to seeds in their feeders to deter squirrels,
raccoons and other mammals while leaving the birds unaffected. This is because, while
mammals have the standard form of TRPV1, activated by both capsaicin and heat, birds
do not respond to capsaicin. When the TRPV1 gene is extracted from birds, a variant
form of TRPV1 is seen, which responds to heat but not capsaicin. Examination of the
sequence of bird DNA indicates that exact location on the inner surface of the cell’s
outer membrane that is necessary for capsaicin binding. Chilli peppers use birds as a
dispersal agent – coevolution between chillies and birds enabled this mutually beneficial
system to develop.
TRP function can have effects on the perception of pain in other ways. Skin that has become
sunburnt causes a series of inflammatory processes in the skin, including the production of
compounds called prostanoids and bradykinin. These chemicals have the property of reducing
the temperature threshold of TRPV1 activation from 43 °C to 29 °C. This results in a typical water
temperature for a bath or shower then feeling too hot, resulting in a painful burning sensation.
Consciousness
Link The cerebral hemispheres make up a larger proportion of the brain and are more highly developed in
The cerebral humans than in other animals. Each hemisphere is divided into four lobes, each lobe being named after
hemispheres of the the bone of the cranium that covers it. The human cerebral cortex has become enlarged, principally
brain are also covered by an increase in total area, with extensive folding to accommodate it within the confines of the skull.
in Chapter C3.1,
Consequently, each hemisphere has a vastly extended surface, achieved by folding with deep grooves.
page 498.
The cerebral hemispheres are responsible for higher order functions. The division of duties of the two
hemispheres is listed in Table C2.2.4.
■ Table C2.2.4 Inputs and control duties in the cerebral hemispheres
hypothalamus
cerebral hemispheres
cerebellum
pituitary gland
cerebral
■ Figure C2.2.17 cortex
The human brain
by grey matter about 3 mm deep and is densely packed with unmyelinated neurons (known
as pyramidal cells). These cells have a mass of dendrites and a very large number of synaptic
connections. Below this, the bulk of the cerebral hemispheres consists of white matter. This is made
up of myelinated neurons that connect the cerebral cortex with the midbrain, hindbrain and spinal
cord. Beneath, the right and left hemispheres are connected by tracts of fibres.
◆ Consciousness: Consciousness is often described as the ‘mind’s subjective experience’. A robot can unconsciously
the qualitative feeling detect conditions such as colour, temperature or sound, whereas consciousness describes the
that is associated with qualitative feeling that is associated with those perceptions, together with the deeper processes of
perceptions such as
colour, temperature or
reflection, communication and thought. The development of brain-scanning technologies such as
sound, together with electroencephalography (EEG), magnetic resonance imaging (MRI) and functional magnetic
the deeper processes of resonance imaging (fMRI), have enabled scientists to research the mechanisms in the brain that are
reflection, communication
associated with the conscious processing of information (Figure C2.2.18).
and thought.
In EEG, electrodes consisting of small metal discs with thin wires are attached to the scalp. The electrodes
detect tiny electrical charges that result from the activity of brain cells. The charges are amplified and
appear as a graph on a computer screen, or as a recording that may be printed out on paper.
Using fMRI, the precise parts of a living, healthy, functioning brain that are activated when a
particular activity occurs can be mapped accurately. This technique is entirely non-invasive.
Furthermore, it can detect activity anywhere in the brain, and with high resolution. Results of a scan
are generated quickly.
MRI uses a powerful magnetic field to produce detailed images.
It works by measuring the way the vast number of hydrogen
atoms present in the body’s water molecules absorb and then
emit electromagnetic energy. The nucleus of each hydrogen atom
(a single proton) is, in effect, a tiny magnet; in a strong magnetic
field, these line up – as compass needles do in a magnetic
field. In the process of a scan, a pulse of radio waves is applied,
sufficient to cause the hydrogen nuclei to change orientation.
When the pulse is switched off, the nuclei revert to their original
orientation and each nucleus emits a signal (at radio frequencies).
■ Figure C2.2.18 Image showing use of fMRI
to provide early detection of consciousness in From this signal, the scanner can work out the three-dimensional
patients with severe traumatic brain injury location of each nucleus.
fMRI is an advanced form of MRI that detects the parts of the brain that are active when the body
performs particular tasks. Brain cells always require energy and a good supply of oxygen, but during
periods of intense activity the demand for these resources increases locally. The scanner can detect
an increase in red blood cell oxygenation at the site of special neural activity; the technique for this is
known as blood oxygen level dependent (BOLD) contrast. The increase in blood flow to the most active
areas is detected due to the difference between signals arising from hydrogen nuclei in water molecules
in the neighbourhoods of (a) oxyhaemoglobin and (b) deoxyhaemoglobin. When the concentration of
oxyhaemoglobin increases, the fMRI signal rises.
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regions of the brain that are most active. This new brain-mapping technique permits us to work out
the spatial organization of human brain function, down to a sub-millimetre level.
Scientists have begun to determine which regions and circuits in the brain are most important for
consciousness. The cerebral cortex has been known to be important for consciousness since the
nineteenth century. However, more recent research has shown that consciousness is not confined
to only one region of the brain, and that various cells and pathways are engaged, depending on the
stimulus. Data collected by fMRI showed that the brains of healthy individuals had more complex
patterns of coordinated signalling that also changed constantly, compared with people in minimally
conscious states and those under anaesthesia. Studies of brain function using people at varying levels
of consciousness provide data that enable us to determine the mechanisms involved.
ATL C2.2D
What is consciousness and how can research on the brain help to answer this question?
Read this article and summarize the main points in a mindmap or poster:
www.nature.com/articles/d41586-018-05097-x
Points you may want to consider:
l What are qualia and can they be meaningfully studied by science?
l What happens to consciousness after an operation on the cerebellum?
l Can a theory of consciousness be developed?
ATL C2.2E
How does the anatomy of the human nervous system compare to that in other animals with a very
different evolutionary origin? Another intelligent animal is the octopus. Read the following article about
the nervous system of an octopus: www.scientificamerican.com/article/the-mind-of-an-octopus
Carry out your own research about this intelligent animal. What is it like to be an octopus?
Produce a short article or poster that summarizes your findings.
LINKING QUESTIONS
1 In what ways are biological systems regulated?
2 How is the structure of specialized cells related to function?