Resting Membrane Potential || How Resting Membrane Potential is Generated?

Under resting conditions, the inside of a cell is electronegative, with a neuron's resting membrane potential typically around -90 mV. The main contributors are the diffusion of potassium (K) through K leak channels and the electrogenic nature of the Na-K ATPase pump.

K leak channels are open during the resting state. Due to a higher concentration of K inside the cell, K diffuses out, making the outside electropositive and the inside electronegative. This is the primary factor in generating resting membrane potential.

The Na-K ATPase pump moves 3 Na ions out and 2 K ions in per cycle, resulting in a net loss of one positive ion from the cell. This also contributes to the inside of the cell becoming electronegative.

The high internal K concentration (140 mEq/L) versus low external (4 mEq/L) drives K out. This creates an internal electronegativity that eventually becomes strong enough to pull K back in, establishing an equilibrium at approximately -94 mV where concentration and electrical gradients are opposing.

While Na tends to diffuse into the cell due to its concentration gradient, Na channels are mostly closed during resting conditions. Therefore, the small amount of Na entry only slightly shifts the voltage towards positive, resulting in a combined potential of -86 mV from K and Na diffusion.

The Na-K ATPase pump contributes about -4 mV to the resting membrane potential because it actively transports more positive ions out of the cell than into it. Although its direct contribution is small, it's crucial for establishing the K gradient, which is the primary driver of resting membrane potential.