2. Specific Learning Objective
At the end of the class, the student should be able to :
• Define resting membrane potential
• Describe the genesis of resting membrane potential
• Describe the ionic basis of RMP
• Discuss Nerst Equation
• Discuss Goldmann-Hodgkin-Katz Equation
3. Introduction
• All living cells have an electrical potential, or
voltage difference, across their membranes,
called as membrane potential.
• Ions arrange themselves along inside and
outside of the cell membrane.
4. RMP
• At resting state of the cell, membrane potential
difference across cell membrane is called
Resting Membrane Potential/Transmembrane
potential.
• Inside of the neuron is negative with respect to
the outside.
• Membrane is said to be polarized.
8. Special feature Continue…
• Converted into action potential in excitable
tissue upon stimulation.
• Decides the degree and duration of action
potential.
• Relatively stable but can fluctuates in
some cells like visceral smooth muscles
9. Concept of RMP
• Selective permeability of cell membrane
• Gibbs Donnan equilibrium
• Nernst Equation
• Goldman-Hodgkin Equation
• Role of Na+ K+ ATPase pump
10. Selective permeability of cell
membrane
• Some are highly permeable, some are
less while other are impermeable.
• Depends on:
Molecular Weight
Size of ion (hydrated)
11. Mol. Wt. and Radius of different
ions (hydrated)
12. Gibbs Donnan equilibrium
• When two solutions containing diffusible
ions across membrane, at equilibrium
each solution will be electrically neutral.
• Total no. of anions is equal to total no. of
cations in each solution.
(K+)A= (Cl-)A and (K+)B = (Cl-)B
14. • Also the product of diffusible ion of one
solution will be equal to the product of
diffusible ion in other solution.
Or
(K+)A X (Cl-)A = (K+)B X (Cl-)B
(K+)A = (Cl-)B
(K+)B (Cl-)A
15. Gibbs Donnan equilibrium
• Thus there will be equal and balanced
distribution of ions at equilibrium.
• Called:
16. But…
• If one or more non-diffusible ions ‘X−’ are
present on one side then the distribution of
diffusible ions will be:
• 1st rule:
• 2nd rule:
(K+)A + (Cl-)A+ (X-) > (K+)B + (Cl-)B
(K+)A X (Cl-)A = (K+)B X (Cl-)B
17. • From the relationship of (1) and (2), it is
found that:
and
(K+)A > (K+)B
(Cl-)A < (Cl-)B
18. Gibbs’–Donnan effect
• Since ICF contains non-diffusible anions
like proteins and organic phosphate.
• According to Gibbs’–Donnan equilibrium
there is an asymmetrical distribution of
diffusible ions across membrane.
19. NERNST EQUATION
• Asymmetrical distribution of diffusible ions
across the cell membrane (more cation
inside) due to the Gibbs’–Donnan
equilibrium results in concentration
gradient.
20.
21. • Now cations (K+) will try to diffuse back
into the ECF from ICF.
• But it is counteracted by the electrical
gradient, which is created due to the
presence of non-diffusible anions inside
the cell.
22. • Thus equilibrium will be reached between the
concentration gradient and the electrical
gradient resulting in diffusion potential
(equilibrium potential) across the cell membrane.
23. • Magnitude of this equilibrium potential can
be determined by the Nernst equation:
• R = Natural gas constant (value is 8.316 joules/ degree)
• T = Absolute temperature
• Z = Valency of ion
• F = Faraday constant (96,500 coulomb/mole)
26. • Integrated role of different ions in the
generation of membrane potential can be
described accurately by the Goldmann’s
constant field equation:
• PK+, PNa+ and PCl- : The permeabilities of
the membrane for K+, Na+ and Cl-
27.
28. ROLE OF NA+ K+ ATPase
PUMP
• Builds concentration gradient.
• Contribute -4mV to RMP
• Pump back the Na+ that diffuses into the
cell and K+ that diffuses out of the
cell(during action potential)
29. RECORDING OF RMP
• The essential instruments used in
recording the activity of an excitable tissue
are:
–Microelectrodes (size <1 μm)
–Electronic amplifiers (magnify potential
changes 1000x)
–Cathode ray oscilloscope
32. Both electrodes
are on the surface
of axon
One electrode
on the surface
and other
inserted inside
the axon
33. Ionic Basis of RMP
• Factors contributing to even distribution of
ions
Random motion-Particles tend to move down
their conc gradient .
Electrostatic pressure-Like repels like,
opposites attract .
• Factors contributing to uneven distribution
of ions
Selective permeability to certain ions
Sodium – Potassium pump
34. Ions Contributing to RMP
• Sodium (Na+)
• Chloride (Cl-)
• Potassium (K+)
• Negatively charged proteins (A-)
– Synthesized within the cell
– Found primarily within the cell
35. The cell/neuron at rest
• Ions move in and out through non-specific
channels
• K+ and Cl- pass readily
• Little movement of Na+
• A- do not move at all (trapped inside).
36. The cell/neuron at rest….
• Equilibrium potential:The potential at which there
is no movement of an ion.
Ion’s Conc. Gradient = Electrical gradient
• Na+ = +60 mV
• K + = -90 mV(same as RMP of cardiomyocyte)
• Cl- = -70 mV (same as RMP of neuron)
• Ca+ = +130mV
37. The cell/neuron at rest…..
• Na + is driven in by both electrostatic force and
its conc gradient.
• K+ is driven in by electrostatic force and out by
its conc gradient.
• Cl- is at its equilibrium
• Sodium –Potassium pump :Active force that
pumps 3 Na+ inside and 2 K+ outside.
38. Summary
• All living cells have an electrical potential, or
voltage, across their outer membranes c/as RMP
• Ions for development of membrane potential are
Na+,K+ and Cl-
• The magnitude of force acting across the cell
membrane on each ion can be analyzed by Nernst
Equation as follows:
E ion = -RT/ZF in Cin/Cout
39. Summary
• The integrated role of different ion in the generation of
membrane potential can be described by GHK equation
• Voltage of membrane potential is determined by the
conc. gradient and membrane permeability of each of
these ions.
• Signal transmission in the nerve is primarily due to
change in the Na+ and K+ permeability and not much
due to change in Cl- permeability
41. Q.1
Most of the ATP generated in nerve cells is
utilized to energize the:
A. Na-Ca exchanger
B. B. H-ATPase in the cell membrane
C. C. Na-K ATPase
D. D. synthesis of proteins
Ans:C
42. Q.2
The normal resting cardiac muscle cell is
most permeable to:
A. Na
B. K
C. Ca
D. Cl
Ans: B
43. Q.3
The membrane potential at which net flux of
an ion across the membrane is zero is
called:
A. resting membrane potential
B. spike potential
C. electrotonic potential
D. equilibrium potential of that ion
Ans: D
44. Q.4
The Nernst potential (also called equilibrium
potential) is positive for:
A. Na and Cl
B. Na and K
C. Na and Ca
D. K and Cl
Ans: C
45. Q.5
The membrane potential of cardiac muscle
cells is most affected by even a small change
in plasma concentration of:
A. Na
B. K
C. Cl
D. Ca
Ans: B
46. Q.6
Hypokalemia would be expected to result in:
A. a more positive RMP
B. a more negative RMP
C. no change in RMP
D. Increase in excitability of cell
Ans:B
47. Q.7
The equilibrium potential of chloride in
mammalian spinal motor neurons is typically
about:
A. + 20 mV
B. minus 40 mV (inside negative)
C. minus 70 mV (inside negative)
D. minus 90 mV (inside negative)
Ans: C
48. Q.8
The resting membrane potential of
ventricular cardiomyocytes is closest to the
equilibrium potential for:
A. sodium
B. chloride
C. potassium
D. calcium
Ans: C
49. Q.9
The resting membrane potential of neurons
is equal to the equilibrium potential of:
A. Na
B. K
C. Ca
D. Cl
Ans: D
50. Q.10
Which one of the following increases
excitability of cardiac muscle?
A. Increase in ECF [K+] from 5 to 10 mM
B. Increase in ECF [K+] from 5 to 70 mM
C. Decrease in ECF [K+] from 5 to 1.4 mM
D. None
Ans:A
