Describe the following:

1. Neuron cell body

- Contains nucleus that is large, spherical, and has a prominent nucleolus

- Contains Nissl substance (free ribosomes and RER in basophilic clumps that extend throughout the soma

- Contains microtubules and neuro laments that form networks within the cytoplasm for intracellular transport and
structural integrity

- Contains lipofuscin granules (residues of lysosomal activity that accumulate with age

- Also contain mitochondria, lysosomes and Golgi

- Membrane is selective which allows for the resting active membrane potentials

2. Dendrites

- single or multiple processes depending on the neuron type

- Function to increase the receptive area, may branch further to increase surface area for synaptic input

- Conduct the impulse towards the cell body

- Same cytoplasmic contents as some except no Golgi

- Vary in length

- Most of the variation in neurons is due to variation in dendritic structure

3. Axons

- One per neuron, but can give o collaterals

• Conduct the impulse away from the soma

• Arises from axon hillock

• No Nissl substance or Golgi

• Axon/axon hillock have microtubules, neuro laments, and mitochondria

• MTs and NFs are oriented longitudinally for functioning in axoplasmic transport (anterograde/retrograde)

• Terminal branches of then axon are called telodendria

• Axon segments

• Initial - short segment originating from axon hillock

• Conductive - longest, may or not be myelinated

• Transmissive - terminal end that divides into telodendria with terminal boutons

4. Classi cation

- Bipolar neurons have an axon and dendrite at opposing poles (sensory of CNI, CNII, CNIIX)

- Pseudo unipolar neurons have one process that bifurcates with one serving an a erent function (dendrites) and the
other serving an e erent (axon) (Ganglia of cranial nerves V, VII, IX, X and dorsal root ganglia)

- Unipolar neurons - Found only in development

- Multipolar neurons have multiple dendrites and one axon; most common type of neuron

• Golgi type I neurons are axons that project from one region of the CNS to another or from the CNS to the periphery

• Cerebral cortex (pyramidal cells)

• Cerebellar cortex (Purkinje cells)

• Lower motor nuclei of CN III, IV, V, VI, VII, IX, X, XII, XII

• Ventral horn of the spinal cord (alpha motor neurons)

• Autonomic ganglia

• Golgi type II neurons have axons that usually stay in one region of the CNS

• Interneurons

5. Synapses

• How neurons communicate with other and with e ector cells

• Synapses are specialized for the transmission of a chemical message in response to an action potential and has 3
components

• Presynaptic membrane, synaptic cleft, postsynaptic cleft

• Can be axodendritic, axosomatic, axoaxonic

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6. Neurotransmitters

• Neurotransmitters are molecules that are released at the presynaptic membrane and activate receptors on the
postsynaptic membrane

• Cholinergic (acetylcholine)

• Amino acids (glutamate, GABA, aspartate, glycine)

• Biogenic amines (norepi/adrenergic, epi, serotonin, dopamine

7. Axonal transport

• Anterograde - carries materials from the soma to axon/dendrites

• Retrograde - carries materials from the axon/dendrites to the soma

Describe the following nerve bers:

1. Unmyelinated

• Not surrounded by myelin sheath

• In the CNS they are bare

• In the PNS a number of bers are embedded in individual recesses (mesaxon) in a single Schwann cell and its basal
lamina

• Very slow conducting bers

2. Myelinated

• Myelinated nerve bers

• Surrounded by myelin sheath (varies in thickness)

• Found in CNS and PNS

• In the PNS the Schwann cells wrap their membranes around a single axon to form a myelin sheath

• There are several Schwann cells (PNS) or oligodendrocytes (CNS) along the length of a single axon

• Junction between two cells is called a node of ranvier

Describe the structure of peripheral nerves

• Peripheral nerves are bundles of myelinated and unmyelinated nerve bers in the PNS

• Peripheral nerves have 3 layers of connective tissue

• Endoneurium - very thin, surrounds the individual nerve bers and their associated Schwann cells

• Perineurium - surrounds a bundle of bers and forms a fascicle

• Epineurium - surrounds the entire nerve (cranial or spinal)

• Within the CNS, the myelinated and unmyelinated nerve bers are not enclosed in connective tussle components

• Why the brain is squishy

• Neurovascular bundle is when an artery, vein, and nerve run adjacent to each other

Describe the following supporting cells of nervous tissue:

1. Satellite cells

• Layer of small cuboidal cells that surround the cell bodies of ganglia

• In the cranial, spinal, and autonomic ganglia

• Provide insulation and serve as a pathway for metabolic exchange

2. Schwann cells

• In the PNS the Schwann cells wrap their membranes around a single axon to form a myelin sheath

3. Glial cells

• Provide structural support and maintenance of local conditions for neurons

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 • Astrocytes, oligodendrocytes, microglia

• In the CNS, glial cells clean up the debris after an injury and seal o the area

• This leaves a glial scar which interferes with regeneration

• More numerous than neurons and are able to proliferate

• Most brain tumors (benign or malignant) are of glial origin

4. Oligodendrocytes

• In the CNS myelin sheath is formed by oligodendrocytes which can myelinate several axons

• Glial cell

5. Astrocytes

• Star shaped cells found in gray and white matter of the CNS

• They have perivascular end-feet that sit on blood vessels and help form BBB

• They also function in physical (provide rigidity) and metabolic support (immediate source of glucose) of neurons

• The cells are part of the healing process (glial formation or gliosis) in the brain and thus can multiply at any time

• Spontaneous local proliferation of astrocytes can lead to brain tumor

• Glial cells

6. Microglia

• Macrophages of the CNS

• Found in both gray and white matter and are mesodermal in origin

• Migrate to the sites of dead neurons and glial cells and phagocytize them

• Regarded as immune protectors of the CNS

• Glial cell

7. Ependyma cells

• Simple cuboidal epithelium that lines the ventricles of the brain and the central canal of the spinal cord

• Modi ed ependymal cells and associated capillaries form the choroid plexus which produces CSF

Give an overview of signaling in the human body

• Several types of molecules function as messengers

• Target cells must have a receptor speci c to the signaling molecule

• Once the receptor is bound, downstream

De ne the neurophysiological terms used in general and Podiatric Medicine and general medicine use of
electricity

Explain how separating charges creates voltage

• Creates potential di erence (membrane potential or Vm)

Explain how the equilibrium/membrane potential is determined

• For each ion, the Eq is determined by its valency and the [ ] of ICF and ECF

• Determines direction and ux

• RMP is determined by the Eq of permeant ions proportional to their permeability

• K is 95%, Na is 5%

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Explain how K+ is involved in creating the resting potential and calculate an equilibrium potential using the
Nernst equation

• At rest there are more anions inside the cell

• K has a greater concentration inside compared to outside but the [anions] inside is greater than K and therefore
override the positive charges of K inside the cell (why the ICF is negative despite K having higher [ ] IC)

• At rest there are more cations outside of the cell

• Na+ is a big contributor, Cl- is also greater on the outside but its concentration is less than the cations so the outside
is still positive

• Result is a negative membrane potential (negative on the inside)

• Because [K+] is higher inside the cell and lower outside the cell, its CONCENTRATION GRADIENT is towards the
outside (~140 mEq/L ICF, 5 mEq/L ECF)

• But since there is a high concentration of cations/positive charge on the outside, potassiums ELECTRICAL GRADIENT
is towards the inside of the cell

• K is positively charged and therefore attracted to the negative environment of the ICF and repulsed by the positive
environment of the ECF

• At -70mV the concentration gradient of K is greater than its electrical gradient, so K+ will move out of the cell and add
1 positive charge to the ECF, while subtracting 1 positive charge from the ICF

• Basically adding +1 to ECF and -1 to ICF per ion

• Results in the -88mV Eq for K

• This means that the concentration gradient and electrical gradient are opposite and equal when the di erence
between inside and outside is -88mV

Predict the direction of change in voltage of the resting membrane potential and action potential when
extracellular ion concentrations or permeabilities are altered

• Hypokalemia is when the ECF [K] is decreased

• This increases the concentration gradient of potassium that wants to push it out of the cell

• Decreases the electrical gradient that wants to push it into the cell (since there is less positive charge in the ECF,
repulsive forces are decreased)

• So you are left with a bigger [ ] gradient and smaller electrical gradient for K than you had at -70, so [ ] gradient wins
and pushes potassium out of the cell

• As more potassium leaves the cell, the ICF becomes more negative while the ECF becomes more positive

• Creates a greater di erence in potential, which decreases the RMP

• Therefore it is hyper polarizing the cell and making it more di cult to reach the threshold

• This also results in your Eq potential for K to decrease since the value at which the [ ] gradient and the electrical
gradient are opposite but equal is more negative than -88

• Hyperkalemia is when the ECF [K] is increased

• This decreases the concentration gradient of potassium that wants to push it out of the cell

• Increases the electrical gradient that wants to push it into the cell (since there is more positive charge in the ECF,
repulsive forces are increased)

• So you are left with a bigger electrical gradient and smaller [ ] gradient for K than you had at -70mV, so electrical
gradient wins and pushes potassium into the cell

• As more potassium enters the cell, the ICF becomes more positive while the ECF becomes more negative

• Creates a smaller di erence in potential, which increases the RMP

• Therefore it is depolarizing the cell and making it easier to reach the threshold

• This also results in your Eq potential for K to increase since the value at which the [ ] gradient and the electrical
gradient are opposite but equal is less negative than -88mV

• Hypercalcemia makes makes the threshold potential more positive (harder to stimulate)

• Hypocalcemia makes the threshold potential more negative (easier to stimulate)

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 Explain the role of the NaK pump in maintenance of gradients and electrogenesis

• Maintains the concentrations of electrolytes across the plasma membrane via active transport

• Na/K ATPase

• Responsible for the repolarization of neurons

Describe voltage-gated Na+ and K+ channels

• Voltage gated Na+ are present in excitable cells

• Respond to a change in membrane potential in time dependent manner

• Have 2 gates called activation and inactivation gates

• During rest, AG is closed and the IG is open

• At the threshold, AG opens, allowing Na to enter along its electrochemical gradient

• After a brief delay all of the IG closes and inhibits further entry of Na+ into the cell (absolute refractory period) - top of
the peak

• As the cell repolarizes some of the IG start to open allowing channels to be stimulated in the presence of a strong
stimulus (relative refractory period)

• However the amplitude of the AP is reduced since there are less gates open (and therefore less Na can enter the cell
and depolarize)

• When the cell is back to RMP, all the IG are open and the AG are closed

• Voltage gated K+ are the largest family of VG ion channels

• Delayed outward recti er causing repolarization

• Time dependent but take longer than Na+ VGC to open in response to depolarization

• Opening of K+ channels allows the movement of K+ out of the cell

• Opens at the peak of the AP during the absolute refractory period

• At the end of repolarization the K+ channels are closing slowly, which allows for a higher amount of K+ to exit the cell
(hyperpolarization)

• Gates are closed when the hyperpolarization is over and the cell is back to RMP

Describe the ionic events when the action potential threshold is crossed

• When the cell reaches -55mV, this triggers the AG on the Na VGC to
open, which allows a large in ux of Na

• This makes the ECF more negative and ICF more positive

• At the peak, K VGC opens and allows for the e ux of K out of the cell

• This starts repolarization

• Also at the peak the IG closes, inhibiting further Na entry

• During repolarization, the Na/K ATPase pumps 3 Na out of the cell and 2
K into the cell to establish the RMP

Explain how transfer of information within the nervous system is

• The stimulus needs to open enough sodium channels to bring the MP to -55mV

• Once -55mV is reached, the AG of other Na channels open allowing further depolarization (positive feedback)

• All or none states that once the threshold is met, all of the gates will open and AP will occur

• If threshold is not met then the AG don’t open and there is no AP

• Cannot increase or decrease the amplitude of the AP (exception is during the RRF) regardless of stimulus size,
because once threshold is met the stimulus doesn’t matter

• Can increase/decrease the frequency of AP

• ARF is when the IG of Na VGC are closed, so no Na can enter the cell and another AP is impossible (from the top of
the peak to the around the threshold)

• RRF is when some of the IG are opening, so AP is possible but a strong stimulus is required and AP amplitude will be
smaller (threshold to end of hyperpolarization)

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 Describe conduction in unmyelinated axons

• Slower, unreliable, or impossible

• AP propagates and regenerates locally and along the entire axon

• More resources (ions, channels, ATP for the Na/K ATPase) are needed

• Because the AP has to regenerate along the whole axon there is greater loss of amplitude

Describe conduction in myelinated axons

• Smaller loss of amplitude, which allows the stimulus to travel further

• AP regeneration occurs only at each node of Ranvier (saltatory conduction)

• Does not propagate locally

• Allows for faster transmission and requires less resources

• Regeneration of AP takes time

List the determinants of conduction speed

• Temperature, diameter of axon, myelination

List the advantages and disadvantages of using myelin on neurons

• Insulation, smaller loss of amplitude, allows for further travel (longer axon), increases transmission speed, less
resources required

Describe the classi cation of muscle

• Muscle is a tissue that is specialized for contraction in order to move the body or individual components of the body

• Classi cation

• Appearance of cells (striated vs non striated)

• Autonomic or somatic

• 3 types

• Skeletal - striated voluntary

• Cardiac - striated involuntary

• Smooth - non striated involuntary

• Sarcolemma - cell membrane

• Sarcoplasm - cytoplasm

• Sarcoplasmic reticulum - smooth ER (sequester Ca+2)

• Sarcomere - functional unit within a myo ber

• Skeletal muscle comprises the muscles of the MSK system and some muscles that do not move bone (diaphragm,
extra ocular, muscles of facial expression)

Describe the structure of skeletal muscle

• Motor unit

• A lower motor neuron (cranial or spinal) and all the skeletal muscle bers it innervates

• Every muscle is innervated by multiple neurons and the ratio of neuron to muscle bers
ranges from 1:1 to 1:100

• The nerve supply to the skeletal muscle is essential for contraction and muscle tone

• Denervation results in accid paralysis, are exia, atonia, and atrophy of muscle

• Endomysium, perimysium, epimysium (dense irregular) are the layers and are continuous
with the tendons/aponeuroses of the muscle

• BV and nerves uses these CT sheaths to reach the muscle

• Each myo ber is multinucleated (nuclei are peripheral)

• SR forms membrane bound tubules that expand into terminal cisterna next to t-tubule

• Triad is located at the junction of A and I bands

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 • F-actin, troponin, tropomyosin - thin laments

• Myosin - thick laments

• Each myosin head has 6 subunits

• 2 myosin heavy chains form the tail and 2 globular heads

• The heads has 3 regions

• Actin binding site, ATP binding site, light chain binding site

• Titin is a large protein that links the thick myo lament to the Z disk and
provides strength and elasticity

• Actin laments insert onto the Z disk via alpha actinin

• Z disks are aligned and linked by intermediate lament proteins between themselves and to the sarcolemma at
specialized plasma membrane regions called costameres

Describe the ner types of skeletal muscle

• Rich blood supply

• Motor - lower motor neurons

• Sensory - dorsal root ganglia (and some cranial nerve ganglia)

• Peripheral process connects to muscle spindles and GTOs

• Sensory and motor neurons are located in the same nerve

Describe the repair of skeletal muscle

• Satellite cells proliferate after injury

• Exercise causes hypertrophy

Describe the structure of cardiac muscle

• Epicardium - composed of mesothelium (visceral layer of pericardium) and CT containing nerves and BVs to the heart

• Myocardium - cardiac muscle

• Inner portion of the myocardium contains specialized bers and Purkinje bers (impulse conduction)

• Endocardium - covers the inner surface of the heart

• Cylindrical cells

• Single centrally located nucleus

• Sarcomeres are the same arrangement as skeletal

• Striated

• T-tubules are larger than skeletal muscle, diads at Z line, more mitochondria

• Intercalated discs - between the ends of adjacent muscle bers

• Anchor points for myo brils, allow for rapid spread of contractile stimulus

Describe the blood supply and innervation of cardiac muscle

• Coronary arteries and their branches

• ANS (PSNS and SNS)

Describe the repair of cardiac muscle

• Destroyed cardiac cells are not replaced by new muscle cells but with brous CT

Describe the structure of smooth muscle

• Spindle shaped

• Single centrally located elongated nucleus

• Not striated

• Contractile proteins are actin, myosin, and intermediate laments

• Invaginations in the membrane are called caveolae (equivalent to T-tubules)

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• Tension generated by contraction is transmitted through the dense bodies to other cells allowing a group of smooth
muscle cells to function as a unit

• Specialized for continuous contractions with low force

• Found in sheets/bundles in the walls of the gut, bile duct, ureters, urinary bladder, respiratory tract, uterus, and BVs

Describe the blood supply and innervation of smooth muscle

• Small arteries in the surrounding CT

• ANS (some are both and some are only SNS)

• Some smooth muscle contracts in response to hormones

Describe the repair of smooth muscle

• Undergoes mitosis or new cells are derived from undi erentiated cells in BVs

• Uterus has regularly replication populations of smooth muscle cells

Describe in sequence the events of muscle contraction proposed by the SFT

• The cell gets depolarized by acetylcholine

• The stimulus travels along the sarcolemma until it reaches the t tubules

• The t tubule is depolarized, which activates DHPRs (VG L type Ca channels)

• Opening of the DHPRs allows extracellular Ca to enter the cell (important for cardiac) and mechanically triggers the
opening of the RYR on the SR membrane

• RYR (Ca channel) opens and allows Ca stored in the SR to enter the sarcoplasm, which results in the increase of [Ca]

• Unique to skeletal muscle, allows for contraction without relying on EC Ca levels

• The Ca binds to troponin C subunit on actin, which causes a conformational change in the troponin

• The change shifts the tropomyosin and uncovers myosin binding sites on actin laments

• Myosin (ADP + Pi) binds to the actin, releasing the Pi (cross bridge)

• It then pulls the actin towards the M-line while releasing the ADP, which is called a power stroke

• An ATP molecule binds to the myosin head and releases it from actin

• Myosin ATPase hydrolyzes the ATP into ADP and Pi and cocks the myosin head the other way

• When IC [Ca] decreases, relaxation occurs

• SERCA (sarcoplasmic and endoplasmic reticulum calcium ATPase) is distributed along the SR
membrane and uses one molecule of ATP to transport 2 molecules of Ca back into the SR

• Ca binding proteins (calsequestrin) inside the SR help bu er the Ca which allows for large
amounts of Ca to be stored in the SR

• Ca is also pumped out of the cell by Ca ATPase and Na/Ca exchanger

List the advantages and disadvantages of glycolytic and oxidative muscle metabolism

• Glycolytic - fast but ine cient

• 2 net ATP

• Pyruvate is converted to lactate

• Can only maintain max muscle contraction for 1-2 mins before byproducts accumulate

• Oxidative - slow but e cient

• 36/38 ATP per glucose

• CO2 and H2O are byproducts

• Can continue inde nitely as long as substrate is available

Identify which metabolic pathway would predominate in certain activities

• Explosive sprint - PC

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Evaluate the determinants of fatigue and strength in skeletal muscles

• Fatigue is a decline in muscle contraction strength (force) and speed (velocity)

• Central - changes in the CNS

• Neuromuscular - abnormal transmission of the signal from the nerve to the muscle

• Muscular - changes in the muscle

Identify the speed and fatigue resistance properties of fast and slow twitch muscles

• SO (type I) - slow, fatigue resistant

• Moderate glycolytic activity

• Contain smaller motor units

• FOG (type IIa) - medium speed and fatigue resistance

• High glycolytic activity

• Contain larger motor units

• Contracts with faster and stronger contraction than SO

• FG (type IIx) - high speed and low fatigue resistance

• Each motor unit innervates multiple bers, but all bers are of the same type

Graph the relation between length and tension and state the relation in terms of the SFT

• Preload - initial stretching of the muscle

• Active tension is the force generated during voluntary agonist muscle contraction

• Parabola e ect because with small/large length the force is not optimal since the sarcomeres
are not lined up

• Passive tension is the stretching of a muscle (when an agonist contracts and the antagonists
has to stretch

• Starts at the peak of active tension and increases exponentially

• Isometric contraction - muscle length is xed but the shortening of sarcomeres increases
tension

• Isotonic contraction - muscle tension is xed but the length of the muscle changes

• Graph between initial length and force show that max force is generated when muscle is at
~ resting length

Graph and explain the load velocity relationship

• After load

• The shortening velocity is inversely proportional to the amount of load it needs to overcome

• At 0 load, muscle shortens with max velocity

• Depends on the rate of cross bridge formation

• Depends on the composition of the muscle (type I, II)

• At max load, velocity is 0

• Isometric contraction

• Depends on total amount of crossbridge formation that can occur

• Loads higher than max load lead to eccentric contraction (directly proportional)

Explain how summation and tetanus can grade the force of contraction

• Temporal summation

• Nerve impulse frequency is increased

• The more frequent APs increase Ca release from the SR

• Allows for more cross bridges and more force

• Tetanus - a contraction that starts before the muscle full relaxes

• Incomplete tetanus - the muscle has a chance to relax slightly

• Complete tetanus - muscle does not relax until stimulation is gone

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 Explain how recruitment of motor units can grade the force of contraction

• Spatial summation/recruitment

• More motor units are recruited and total strength is increased

• Order of motor unit recruitment follows the size principle

• Smaller motor units are recruited rst and larger motor units are recruited as needed

Explain how the safety factor ensures that a motor neuron signal causes a skeletal muscle to contract

• Neurotransmitter is released in excess, ensuring su cient binding to the post synaptic membrane

De ne denervation hypersensitivity, atrophy, and contracture

• Growing - muscles lengthen by adding more sarcomeres in series

• Increases length, allows them to shorten more and with a faster velocity

• Hypertrophy - increases the number of myo brils in each muscle cell

• Hyperplasia - increases the number of myo ber in each muscle

• Hypertrophy and hyperplasia add sarcomeres in parallel

• Increases the max force, does not a ect their shortening length or velocity

• When a nerve is damaged, the muscle innervated by that nerve loses its tone and paralyzed

• Acetylcholine is released from the presynaptic membrane of damaged nerve causing small, random, contractions
(fasciculations)

• After several days brillation develops as a result of hypersensitivity to ACh (hypersensitivity denervation)

• Due to the spread of the AChR from just motor end plate to throughout the sarcolemma

• Manifests as spontaneous, repetitive contractions of the muscle

• Denervation also causes atrophy

• These changes can be reversed if the muscle is reinnervated within a few months

• If not, muscle will be replaced by adipose brous tissue resulting in permanent shortening and deformity

• Contracture

Describe mechanoreceptors

• Muscle spindles - run parallel to bers and detect rate of stretch

• Sudden stretch triggers AP and stretch re ex (monosynaptic re ex) is stimulated

• Length is continuously adjusted to ensure they are able to respond to stretching at any muscle
length

• Also play a role in maintaining a basal level of contractile activity (muscle tone)

• Golgi tendon organs - located inside the tendons

• Sense the tension of the muscle and send that information to the brain

• Involved in bisynaptic re ex arcs that prevent muscle injury by inhibiting contraction

Give a synopsis of how EMG is performed

• Uses 2 electrodes to detect electrical potential di erences

• Can pick up compound muscle action potential from muscles located between the recording electrodes

• Signal is ampli ed and analyzed

Name a disease for which EMG might con rm the diagnosis

• MS, myasthenias, neuropathies, myotonia, myopathies,

Distinguish between the functions of multi unit and unitary smooth muscle

• Multiunit - may contract independently of its neighbours due to lack of electrical connection via gap junctions

• Each multiunit smooth muscle myocyte is then required to be innervated by a neuron which makes them capable of
ner control

• Iris, ciliary muscles

• Unitary - electrically coupled via gap junctions; all cells in unitary smooth muscle contracts together as one unit
(function synctium) by the di usion of ions (and propagation of depolarization) through gap junctions

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 • Allows for coordinated but less speci c contraction

• Urinary bladder, GI tract

State the physiological characteristics that help distinguish between smooth, cardiac, and skeletal muscle

• Smooth muscle in some organs maintain a level of contractile force (tone) at all times and are called tonic smooth
muscles

• Sphincters, airways, BVs

• Phasic smooth muscles contract rhythmically or transiently upon stimulation

• Can be stimulated by nervous, humoral, and mechanical stimuli

• Some stimuli can cause a contraction without a signi cant change in membrane potential

• APs can be in many forms

• Simple spike

• A spike followed by a plateau

• Slow wave with a series of spikes on top

Compare the excitation contraction coupling and the biochemistry of the contractile cycle in skeletal and smooth
muscle

• Depolarization phase of smooth muscle relies on Ca instead of Na, which results in slower depolarization

• For contraction phase, it is more reliant on extracellular calcium (skeletal is intracellular)

• EC Ca enters through VGC channels on the membrane

• IC Ca binds to the RYR which causes release of SR Ca

• Known as Ca induced Ca release

• 2nd messenger mediated Ca release from SR by IP3

• This is how smooth muscle can contract without change in membrane potential

• Reduction in Ca is achieved by similar mechanism to skeletal muscle

• SERCA pumps Ca back into the SR

• Na - Ca exchanger ATPase pumps Ca into the ECS

• Regulatory site for SM contraction is myosin molecule (skeletal is troponin)

• SM cells contain a Ca binding molecule similar to troponin called calmodulin in the sarcoplasm

• When [Ca] increases, 4 Ca molecules bind to calmodulin and form a Ca-calmodulin complex (CaCM)

• CaCM binds to and activates myosin light chain kinase (MLCK)

• MLCK phosphorylates the regulatory light chain on the neck of the myosin which causes a conformational change of
the myosin molecule

• Increases its ATPase activity which also cross bridges and contraction to occur

• Contraction speed is slow because MLCK phosphorylation and activation of myosin ATPase is slow

• Myosin ATPase also has slower rate of activity (slower isoforms expressed in SM)

• Relaxation requires myosin light chain phosphatase (MLCP) which dephosphorylates the regulatory light chain of
myosin

• Tonic SM can maintain a high level of tension while keeping the energy expenditure low

• Called the latch state

Describe the various patterns that smooth muscles use to excite a mechanical contraction

• Muscles in hollow organs are sensitive to mechanical force

• Auto-regulation of BVs (increase in blood pressure (stretching of the vessel) leads to vasoconstriction

• Reducing its tension causes vasodilation

• In some organs (mainly storage), stretching causes an initial contraction of the organ followed by a gradual relaxation

• Known as stress relaxation

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