Resting Membrane Potential (RMP)

Dr. Mudassar Ali Roomi (MBBS, M. Phil.)

Important channels or carriers involved in the electrical activity of the cell

Na+, K+ Leak channels: these are open all the time. Involved in generation of resting membrane potential (RMP). Gated channels: these channels open and close at a specific time when needed. Not open all the time. All of the gated channels are closed at RMP 1. Voltage gated channels e.g. voltage gated sodium, potassium, calcium channels. 2. Ligand gated channels e.g. Acetylcholine gated channels at neuromuscular junctions. Sodium-potassium ATPase pump: it works all the time. Also contributes to generation of resting membrane potential. NUTSHELL: Both leak channels and Na+/K+ pump are active at rest ***
17 January 2013 2

Resting Membrane Potential

Definition: it is the potential difference across cell membrane at rest: it is negative inside with respect to outside. Potential values of RMP vary in various excitable tissues: In nerve fiber: -90 mV In skeletal muscle: -90 mV In cardiac muscle: -85 mV SA node: -55 mV In nerve cell body: -70 mV In smooth muscle: -55 mV to -60 mV

Mechanism of Generation of RMP

1. Contribution of the Potassium Diffusion Potential (-94 mVolts) 2. Net Contribution of Sodium Diffusion Through the Nerve Membrane (+8 mVolts) 3. Contribution of the Na+-K+ Pump (-4 mVolts)

Mechanism of Generation of RMP

Mechanism of regulation of RMP

K+

OUTSIDE

Na+ 140 mEq / L 14 mEq / L

4 mEq / L 140 mEq / L INSIDE

Na+ IS 10 TIMES > OUTSIDE THAN INSIDE K+ IS 35 TIMES > INSIDE THAN OUTSIDE K+ WILL TEND TO DIFFUSE OUT & Na+ WILL TEND TO DIFFUSE IN. INSIDE CELL MEMBRANE ARE PROTEIN CHANNELS (LEAK / VOLTAGE / LIGAND GATED) K+ , Na+ LEAK CHANNELS ARE 100 TIMES MORE PERMEABLE TO K+ THAN TO Na+. SO MAIN MOVEMENT IS K+ OUTFLUX WHICH CONTRIBUTES TO RMP (negative inside)

Mechanism of regulation of RMP

Another factor is Na+-K+ pump (active all the time). Pumps out 3 Na+ ions & Pumps in 2 K+ ions. So more electro-positive ions are pumped out & contributes to RMP. As membrane is more permeable to K+ at rest, & much ionic diffusion, so large amount of K+ should move out, but net movement is not much. Why???

Mechanism of regulation of RMP

This is because when K+ moves out, anions (non-diffusible: proteins, organic phosphate & organic sulfate anions) attract them back. But this movement is sufficient to cause relative electro-negativity inside the membrane. Out of -90mV, -86mV is due to K+ outflux & -4 mV is due to Na+ K+ pump. What is the evidence???

Evidence of major contribution to RMP by K+ ion:

If we change, [K+] in ECF RMP is disturbed. If there is hypo-kalemia in ECF RMP will become more negative due to more potential difference hyper-polarization (more K+ leak out than resting level). If there is hyper-kalemia RMP becomes less negative hypo-polarization. But changes in [Na+] in ECF has no significant effect on RMP. We can also prove this by Nernst Equation.

Nernst Equation
EMF (mV) = +/- 61 log conc inside / conc outside Assume that at rest, cell membrane is highly permeable to Na+, then: -61 log 14/140 (- for Na+ & K+ & + for Cl-) = -61 log 0.1 = -61 x -1 = + 61 mV So potential difference across cell membrane should be +61mV, which is wrong.

 Assume that at rest, cell membrane is highly permeable to K+, then: - 61 log 140 / 4 = -61 log 35 = -61 x 1.54 = -94 mV So this assumption is correct that at rest, cell membrane is highly permeable to K+.

Goldman Hodgkin-Katz Equation

EMF (mV) = - 61 log C Na+ i P Na+ + C K+ i
P K+ + C Cl- o P Cl-

C Na+ o P Na+ + C K+ o P K+ + C Cl- i P Cl(C = CONCENTRATION, P= PERMEABILITY)

WITH GOLDMAN EQUATION SUMMATED POTENTIAL = -86 mV

 K+ Na+ leak channels are highly permeable to K+ but there is some inward movement of Na+ + 8 mV potential is generated. -94 mV is due to K+ efflux + 8 mV is due to Na+ influx -94 + 8 = -86 mV = Goldman potential -4 mV is due to Na+ K+ pump -86 4 = -90 mV = RMP.

UNITS OF EXCITABILITY

1. RHEOBASE 2. UTILIZATION TIME 3. CHRONAXIE

RHEOBASE, UTILIZATION TIME, CHRONAXIE

RHEOBASE: Voltage / strength of stimulus required just to excite the tissue, e.g., 1 mV. UTILIZATION TIME: The time for which Rheobase must be applied to excite the tissue. CHRONAXIE: A time for which a stimulus, double the rheobase when applied, just excites the tissue, e.g., 2 mV. (Chronological is from time).

CLINICAL APPLICATION / SIGNIFICANCE OF CHRONAXIE

A particular value of it for a particular tissue. Type A nerve fiber has minimum value of chronaxie, i-e., they are more excitable as compared to cardiac muscle. (less chronaxie more excitability) In nerve injury repair procedure We assess the recovery by finding chronaxie of nerve effected & muscle effected. It improves with recovery. Damage to nerve fiber is determined by measuring chronaxie.