Q4 LONG ANSWER 10M ★ High-yield

Define resting membrane potential. Describe its ionic basis and the factors responsible for it. Add a note on the Nernst equation.

Physiology · 1st Professional — Pre-Clinical

Definition

Resting membrane potential (RMP) = the steady potential difference across the cell membrane of an excitable cell at rest, the inside being negative to the outside.

Cell	RMP
Large nerve fibre	−70 mV
Skeletal muscle	−90 mV
Cardiac ventricular muscle	−90 mV
SA node	−55 to −60 mV
Smooth muscle	−50 to −60 mV

Factors Responsible

1. Unequal ion distribution across the membrane

2. Selective permeability — membrane at rest is 50–100× more permeable to K+ than to Na+

3. Na+–K+ pump — electrogenic

4. Non-diffusible intracellular anions — proteins, phosphates

Genesis of RMP

A. Contribution of K⁺ (the main factor)

High intracellular K+ (140 mEq/L) → K+ leaks out through leak channels → Anions (protein) cannot follow → Inside becomes negative → Electrical attraction opposes further K+ exit → Equilibrium reached

K+ equilibrium potential (EK) = −90 mV

B. Contribution of Na⁺

Small inward leak of Na+ makes the interior slightly less negative
ENa = +61 mV
Shifts RMP from −90 mV to about −86 mV

C. Contribution of the Na⁺–K⁺ pump

3 Na+ out : 2 K+ in → net loss of positive charge
Adds a further −4 mV → final RMP −90 mV

Quantitative Contribution to RMP

Factor	Contribution
K+ diffusion potential	−94 mV
Na+ diffusion potential	+61 mV (but permeability very low)
Net diffusion potential	−86 mV
Na+–K+ pump (electrogenic)	−4 mV
Final RMP	−90 mV

Measurement of RMP

Two electrodes — one inside the cell, one outside
Intracellular electrode = glass microelectrode, tip < 1 µm, filled with 3M KCl
Connected to a cathode ray oscilloscope through an amplifier
First recorded by Hodgkin and Huxley in the giant axon of the squid

Nernst Equation

Eion = (61 / z) × log10 ([ion]outside / [ion]inside) mV at 37°C

Gives the equilibrium potential for a single ion
Goldman–Hodgkin–Katz equation accounts for all permeant ions and their relative permeabilities

Ionic Basis Summarised

Ion	ECF	ICF	Equilibrium potential
Na+	142	10	+61 mV
K+	4	140	−90 mV
Cl−	103	4	−70 mV
Ca2+	5	< 1	+130 mV

Terms Related to Membrane Potential

Term	Meaning
Polarised	Membrane at resting potential; inside negative
Depolarisation	RMP becomes less negative → excitability ↑
Hyperpolarisation	RMP becomes more negative → excitability ↓
Repolarisation	Return towards RMP
Firing level (threshold)	About −55 mV; the potential at which an action potential is triggered

Applied Aspects

Hyperkalaemia → ↑ extracellular K+ → RMP becomes less negative (depolarised) → initial hyperexcitability, then inactivation of Na+ channels → cardiac arrest in diastole
Hypokalaemia → RMP more negative (hyperpolarised) → muscle weakness, paralysis
Hypocalcaemia → ↑ Na+ permeability → hyperexcitability → tetany
Ouabain / digitalis → pump inhibition → gradual loss of RMP

CLINICAL PEARL

Note: RMP is essentially the K+ equilibrium potential, modified slightly by Na+ leak and the electrogenic pump. This is why serum K+ disturbances are so dangerous to the heart.

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