BIOLISTRIK
MEMBRANE POTENTIAL AT REST AND DURING ACTIVITY
Concentrations of Biological Substances
Traditionally, the concentrations were
expressed in mg/100 ml. It is still used,
but molecular weight of different
substances are different. Therefore,
although concentrations of substance A
and B in blood may be M mg/100 ml
each, the number of molecules of each
in 100 ml of blood will be different.
Since, substances interact in terms of
molecules expressing the concentration
in terms of mass/volume (e.g. mg /100
ml) is no longer considered to be best
mode of expression. Currently popular
modes of expressing concentrations are:
1. Moles/L
2. Equivalents/L
3. Osmols/L.
For small concentrations suitable units
are:
i. millimoles/L
ii. milliequivalents/L
iii. milliosmols/L
Abbreviations
m Mol/L
mEq/L
mOsm/L.
1. One mole of substance is = to its
molecular weight in grams, e.g. 1 mole
of NaCl = 58.5 g of NaCl.
2. Equivalent weight of a substance is in
relation to its participation in chemical
reactions, e.g. 1 molecule of HCl will
completely neutralize one molecule of
NaOH but a molecule of H 2SO4 is
enough to neutralize 1 molecule of
NaOH. Equivalent weight of HCl will be
equal to its molecular weight but that of
H2SO4 will be half its molecular weight.
In case of acids and alkalis, when the
concentration is 1 gram equivalent
weight/ 1L it is called a 'Normal' or 1 N
solution.
3. Osmolarity of a substance is in
relation to the osmotically active entities
that its molecule provides. One molecule
of NaCl provides two osmotically active
entities Na+ and Cl-. Thus, 180 g/L of
glucose (an unionized compound) is
equal to 1 mole/L and also 1 osmols/L.
But 58.5 g/L of NaCl is equal to 1 mole/
L, but is= 2 osmoles/L.If instead of
volume of the solvent, concentration is
expressed in terms of mass of
the solvent, the concentration is called
molal or osmolal concentration.
Thus, molality of a solution is its
concentration in moles/kg and
osmolality is concentration in osmols/kg.
Since volume is affected by temperature
but the mass is not, molality and
osmolality are independent of
temperature.
Membrane Potential at Rest
Most living cells show some difference in
electrical potential across the cell
membrane. This difference is called
membrane potential. Excitable cells, i.e.
muscle and nerve cells - show: (a)
membrane potential while at rest, but
also show (b) a dramatic change in the
potential during activity.
GENESIS OF RESTING MEMBRANE
POTENTIAL (RMP)
RMPmay be measured by means of
fine intracellular glass electrode filled
with solution of KCl, with a tip diameter
less than 1 micron, which can penetrate
the excitable tissue without causing too
much injury (Fig. 6.1). As compared to
the ECF the interior of the cell is
electrically negative.

RMP is mainly the result of following
factors:
1. Difference between intracellular and
extracellular potassium concentration.
2. Impermeability to protein ions.
3. Poor permeability of the membrane to
sodium ions.
4. Sodium pump.
Let Us Explain
In living cells the major intracellular
negative ions are protein ions at
physiological pH. These protein ions
cannot diffuse out of the cell, because
the membrane is not permeable to
them. Inside the cell the positively
charged potassium ions will try to
diffuse outward due to concentration
gradient, through the leak channels in
the cell membrane. But the negatively
charged protein ions cause them to
diffuse inwards. A point will be reached
when outward movement of potassium
ions will be exactly balanced by their
inward movement. From this point
onward there will be no net diffusion of
the potassium ions. The potential
difference at this point will be called
equilibrium potential. At equilibrium
potential potassium ion concentration in
a mammalian muscle cell is:
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
Sodium in a mammalian muscle cell, the
sodium ion concentration is:
12 m Eq/L in ICF, and
145 m Eq/L in ECF.
The concentration gradient as well as
electrical gradient favor the diffusion of
sodium ion in the cell. This extremely
strong tendency is neutralized by the
sodium pump, which is present in the
cell membrane. Na pump is a carrier
mediated active transport mechanism
located in the cell membrane.
Carrier for the pump is Na K ATPase
which means that the carrier protein
binds with both sodium and potassium
ions and also acts as an enzyme for
hydrolysis of ATP. Hydrolysis of ATP
generates energy which drives the
pump. The mechanism pumps 3 sodium
ions out of the cell in exchange for 2
potassium ions which are pumped into
the cell. Since the number of positive
ions pumped out exceeds, those
pumped in, the pump generates an
electrical potential across the cell
membrane. That is why the pump is also
referred to as electrogenic sodium
pump. This pump neutralizes the
passive leakage of sodium ions into the
cell through pores in the membrane,
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
value, it leads to a well defined electrical
change known as action potential (If
magnitude of depolarization is below a
certain threshold value, it gradually
fades away).
1. Thus, action potential is a brief
depolarization of large magnitude
followed by repolarization.
2. There is a change in the membrane
potential from about 90 mv to +30mv
during action potential.
3. Repolarization means return of
membrane potential to the RMP (90
mv).
4. Because action potential is a brief
depolarization
of large magnitude it is known as spike.
Towards the end of action potential
there may be long lasting phases of
deviation from RMP before the
membrane potential finally
settles down at RMP. These deviations
are
known as after potentials, which are of
two
types:
1. Negative after potential, and
2. Positive after potential.
Action potential is generated by
sequential
changes in membrane permeability to
sodium
and potassium ions, due to opening up
of
voltage gated channels for sodium and
potassium sequentially (Fig. 6.3).
The sequence of events are (Fig. 6.4):
1. Stimulus of excitable tissue leads to
immediate increase in the permeability
to
sodium due to opening of voltage gated
channels of sodium to about 5000 times.
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
inactivation gate is open.
At suprathreshold depolarization
opening of activation gate and closure of
inactivation gate takes place.
But opening of activation gate is quick,
while the closure of inactivation gate is
delayed. That is why there is a short
interval
during which both components of the
gate are
openthis leads to action potential.
Potassium Channels
They are simple channels:
1. In response to a suprathreshold
depolarization
the voltage gated potassium channels
open with slow time course.
2. Opening of potassium channels
coincides
with closure of the inactivation gate of
sodium channel. Both these processes
contribute to repolarization and restore
the
RMP.
3. At RMP the potassium channel close
automatically.
In summaryaction potential consists
of:
1. Depolarization of large magnitude
followed by
2. Repolarization, and (i) depolarization
is
due to influx of Na ions whereas (ii)
repolarization is due to efflux of K ions
aided by the fact Na influx is declined.
Characteristics of Action Potential
1. It is all or none change.
2. It has a fixed value.
It is propagated without decrease in its
value.
4. It is uniquely biological phenomenon
and
it is seen only in living excitable cells.
5. One action potential must be
complete
before second one is induced. Therefore,
excitable tissues have refractory period.
6. Action potential cannot be fused
together
or superimposed on each other.
After potentials (See Fig. 6.2) towards
the
end of action potential there are phases
of
small deviation from RMP, before the
membrane potentials finally settles
down at
RMP. These deviations are known as
after
potentials:
1. Negative after potential: Towards the
end of
action potential, membrane potential
remains less negative than RMP for a
short
while. This is known as negative after
potential. Cause for it is excess
potassium
accumulate outside the cell membrane.
Hence, diffusion of potassium ions out of
the cell becomes slow.
2. Positive after potential: After a phase
of
negative after potential the membrane
potential becomes more negative than
RMP
for sometime. This is known as positive
after potential.
Cause for it:
i. Excess potassium permeability
continues
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.