BIOLISTRIK

MEMBRANE POTENTIAL AT REST AND DURING ACTIVITY

Concentrations of Biological Substances

Traditionally, the concentrations were that its molecule provides. One molecule
expressed in mg/100 ml. It is still used, of NaCl provides two osmotically active
but molecular weight of different entities Na+ and Cl-. Thus, 180 g/L of
substances are different. Therefore, glucose (an unionized compound) is
although concentrations of substance A equal to 1 mole/L and also 1 osmols/L.
and B in blood may be M mg/100 ml But 58.5 g/L of NaCl is equal to 1 mole/
each, the number of molecules of each L, but is= 2 osmoles/L.If instead of
in 100 ml of blood will be different. volume of the solvent, concentration is
Since, substances interact in terms of expressed in terms of mass of
molecules expressing the concentration the solvent, the concentration is called
in terms of mass/volume (e.g. mg /100 molal or osmolal concentration.
ml) is no longer considered to be best
mode of expression. Currently popular Thus, molality of a solution is its
modes of expressing concentrations are: concentration in moles/kg and
1. Moles/L osmolality is concentration in osmols/kg.
2. Equivalents/L Since volume is affected by temperature
3. Osmols/L. but the mass is not, molality and
For small concentrations suitable units osmolality are independent of
are: temperature.
i. millimoles/L
ii. milliequivalents/L Membrane Potential at Rest
iii. milliosmols/L
Abbreviations Most living cells show some difference in
m Mol/L electrical potential across the cell
mEq/L membrane. This difference is called
mOsm/L. membrane potential. Excitable cells, i.e.
1. One mole of substance is = to its muscle and nerve cells - show: (a)
molecular weight in grams, e.g. 1 mole membrane potential while at rest, but
of NaCl = 58.5 g of NaCl. also show (b) a dramatic change in the
2. Equivalent weight of a substance is in potential during activity.
relation to its participation in chemical
reactions, e.g. 1 molecule of HCl will
completely neutralize one molecule of GENESIS OF RESTING MEMBRANE
NaOH but a molecule of H 2SO4 is POTENTIAL (RMP)
enough to neutralize 1 molecule of RMPmay be measured by means of
NaOH. Equivalent weight of HCl will be fine intracellular glass electrode filled
equal to its molecular weight but that of with solution of KCl, with a tip diameter
H2SO4 will be half its molecular weight. less than 1 micron, which can penetrate
In case of acids and alkalis, when the the excitable tissue without causing too
concentration is 1 gram equivalent much injury (Fig. 6.1). As compared to
weight/ 1L it is called a 'Normal' or 1 N the ECF the interior of the cell is
solution. electrically negative.
3. Osmolarity of a substance is in
relation to the osmotically active entities
 155 m Eq/L in ICF.
4 m Eq/L in ECF.
Difference in potassium concentration
between the intracellular and
extracellular fluid is due to presence of
impermeable negatively charged protein
ions inside the cell.

Chloride
Chloride in a mammalian muscle cell,
chloride Fig. 6.1: Measurement of RMP ion
concentration is:
4 m Eq/L in ICF, and
120 m Eq/L in ECF.
Chloride is the only major anion to which
the cell membrane is freely permeable.
Its concentration adjusts itself passively
to the potassium equilibrium potential.

Sodium
RMP is mainly the result of following Sodium in a mammalian muscle cell, the
factors: sodium ion concentration is:
1. Difference between intracellular and 12 m Eq/L in ICF, and
extracellular potassium concentration. 145 m Eq/L in ECF.
2. Impermeability to protein ions. The concentration gradient as well as
3. Poor permeability of the membrane to electrical gradient favor the diffusion of
sodium ions. sodium ion in the cell. This extremely
4. Sodium pump. strong tendency is neutralized by the
sodium pump, which is present in the
Let Us Explain cell membrane. Na pump is a carrier
In living cells the major intracellular mediated active transport mechanism
negative ions are protein ions at located in the cell membrane.
physiological pH. These protein ions Carrier for the pump is Na K ATPase
cannot diffuse out of the cell, because which means that the carrier protein
the membrane is not permeable to binds with both sodium and potassium
them. Inside the cell the positively ions and also acts as an enzyme for
charged potassium ions will try to hydrolysis of ATP. Hydrolysis of ATP
diffuse outward due to concentration generates energy which drives the
gradient, through the leak channels in pump. The mechanism pumps 3 sodium
the cell membrane. But the negatively ions out of the cell in exchange for 2
charged protein ions cause them to potassium ions which are pumped into
diffuse inwards. A point will be reached the cell. Since the number of positive
when outward movement of potassium ions pumped out exceeds, those
ions will be exactly balanced by their pumped in, the pump generates an
inward movement. From this point electrical potential across the cell
onward there will be no net diffusion of membrane. That is why the pump is also
the potassium ions. The potential referred to as electrogenic sodium
difference at this point will be called pump. This pump neutralizes the
equilibrium potential. At equilibrium passive leakage of sodium ions into the
potential potassium ion concentration in cell through pores in the membrane,
a mammalian muscle cell is: referred to as leak channels, which
occurs due to electrical as well as
concentration gradient. As it is cell
membrane is poorly permeable to
sodium ions.
At RMP the Na influx through leak
channels is exactly equal to sodium
efflux due to sodium pump.

Action Potential (Fig. 6.2)

A resting nerve or muscle cell becomes
active as a result of stimulus.
Irrespective of the nature of stimulus the
response ischange in the membrane
potential. Membrane becomes less
polarized (for example, from 90 mv to
70 mv) which is known as
depolarization. If the magnitude of
depolarization exceeds the threshold settles down at RMP. These deviations
value, it leads to a well defined electrical are
change known as action potential (If known as after potentials, which are of
magnitude of depolarization is below a two
certain threshold value, it gradually types:
fades away). 1. Negative after potential, and
1. Thus, action potential is a brief 2. Positive after potential.
depolarization of large magnitude Action potential is generated by
followed by repolarization. sequential
2. There is a change in the membrane changes in membrane permeability to
potential from about 90 mv to +30mv sodium
during action potential. and potassium ions, due to opening up
3. Repolarization means return of of
membrane potential to the RMP (90 voltage gated channels for sodium and
mv). potassium sequentially (Fig. 6.3).
4. Because action potential is a brief The sequence of events are (Fig. 6.4):
depolarization 1. Stimulus of excitable tissue leads to
of large magnitude it is known as spike. immediate increase in the permeability
Towards the end of action potential to
there may be long lasting phases of sodium due to opening of voltage gated
deviation from RMP before the channels of sodium to about 5000 times.
membrane potential finally Therefore, large influx of sodium ions
takes
place as: (a) concentration gradient of
sodium, and (b) negativity of the inside
of
the resting cell, both factors favor inflow
of sodium.
2. Increased permeability of sodium
lasts only
for a short while then it declines.
3. When sodium permeability starts
declining
the membrane permeability to channel is open or closed depends on
potassium the voltage. At the resting membrane
ions start increasing as the voltage potential the
gated channels are closed. When the
channels of potassium now open up. membrane
depolarization is beyond a certain
threshold
value the channels open: (a)
temporarily, and
(b) with fixed time course which is
different for
sodium and potassium. These voltage
gated
channels are different than leak
channels.

Since the concentration of potassium

is higher inside the cell, and
ii. Outside of the cell is negative at the
peak of action potential.
Hence, potassium ions diffuse out and Sodium Channel
bring the membrane potential back to Voltage gated sodium channel opens
normal. RMP is restored. promptly
In short depolarization is due to entry at super threshold depolarization (Fig.
(influx) of sodium ions and repolarization 6.5).
is due to exit (efflux) of potassium ions. This increases the permeability to
4. At the end of the action potential the sodium 5000
excitable cell has more sodium ions and times and massive influx of sodium ions
less takes
potassium ions than at the beginning. placein accordance with electrical and
Bringing the concentrations back concentration gradient
towards (=electrochemical
the original is the job of the sodium gradient). Large influx of sodium ions
pump, renders
which it does slowly. the Na pump ineffective and there is
Voltage Gated Channels explosive
By now, we know that action potential is change of membrane potential from 90
triggered by membrane depolarization mv
above to +30 mv. Then, there is inactivation of
a threshold value. sodium channels. Therefore, there is
This is due to existence of voltage gated decrease
sodium and potassium channels in the in sodium permeability.
membrane. Voltage gated sodium channel has two
Voltage gated means that, whether the components: (a) the activation gate, and
(b)
inactivation gate.
At RMPactivation gate is closed and 4. It is uniquely biological phenomenon
inactivation gate is open. and
At suprathreshold depolarization it is seen only in living excitable cells.
opening of activation gate and closure of 5. One action potential must be
inactivation gate takes place. complete
before second one is induced. Therefore,
excitable tissues have refractory period.
But opening of activation gate is quick, 6. Action potential cannot be fused
while the closure of inactivation gate is together
delayed. That is why there is a short or superimposed on each other.
interval After potentials (See Fig. 6.2) towards
during which both components of the the
gate are end of action potential there are phases
openthis leads to action potential. of
Potassium Channels small deviation from RMP, before the
They are simple channels: membrane potentials finally settles
1. In response to a suprathreshold down at
depolarization RMP. These deviations are known as
the voltage gated potassium channels after
open with slow time course. potentials:
2. Opening of potassium channels 1. Negative after potential: Towards the
coincides end of
with closure of the inactivation gate of action potential, membrane potential
sodium channel. Both these processes remains less negative than RMP for a
contribute to repolarization and restore short
the while. This is known as negative after
RMP. potential. Cause for it is excess
3. At RMP the potassium channel close potassium
automatically. accumulate outside the cell membrane.
In summaryaction potential consists Hence, diffusion of potassium ions out of
of: the cell becomes slow.
1. Depolarization of large magnitude 2. Positive after potential: After a phase
followed by of
2. Repolarization, and (i) depolarization negative after potential the membrane
is potential becomes more negative than
due to influx of Na ions whereas (ii) RMP
repolarization is due to efflux of K ions for sometime. This is known as positive
aided by the fact Na influx is declined. after potential.
Cause for it:
Characteristics of Action Potential i. Excess potassium permeability
1. It is all or none change. continues
2. It has a fixed value. leading to negativity inside the
cell.
ii. Sodium pump becomes active again
pumping sodium out.
Propagation of Action Potential
Action potential is propagated without
decrement along the membrane of the
excitable cell.

It is propagated without decrease in its

value.