The Resting Membrane Potential

Core Concept

The resting membrane potential is the steady voltage across a cell's membrane when it is not signaling — about −70 mV in a typical neuron (inside negative). It arises because the membrane is far more permeable to K⁺ than to other ions, and intracellular K⁺ is much higher than extracellular K⁺: K⁺ leaks outward through K⁺ leak channels, leaving behind uncompensated negative charges, until the resulting electrical force balances the outward concentration drive. The Na⁺/K⁺ ATPase does not generate this potential directly; it maintains the Na⁺ and K⁺ concentration gradients on which the potential depends (and adds a small direct electrogenic contribution).

Key Components

Selective permeability

At rest the membrane is ~25–100× more permeable to K⁺ than to Na⁺ (through constitutively open K⁺ leak channels), so K⁺ dominates the potential.

K⁺ leak channels

Channels open at rest that let K⁺ move down its concentration gradient; their efflux makes the inside negative.

Nernst equation

For a single ion, the equilibrium potential E_ion = (RT/zF)·ln([ion]_out/[ion]_in). For K⁺ (roughly 5 mM out, 140 mM in, 37 °C), E_K ≈ −90 mV.

Goldman (GHK) equation

For a membrane permeable to several ions, weights each ion's contribution by its permeability (P): the resting potential is set mainly by the P_K-weighted K⁺ term, with smaller contributions from Na⁺ and Cl⁻, landing near −70 mV rather than −90 mV.

Na⁺/K⁺ ATPase

Actively pumps 3 Na⁺ out and 2 K⁺ in per ATP, keeping [K⁺] high inside and [Na⁺] high outside; its 3:2 electrogenic stoichiometry directly contributes only a few millivolts.

Mechanism

The potential is a diffusion potential. Because K⁺ channels are open and Na⁺ channels are mostly closed, K⁺ leaves the cell down its concentration gradient. Each K⁺ that exits leaves a negative counter-ion behind, so the inside becomes increasingly negative. This electrical field pulls K⁺ back in. Net K⁺ efflux continues until the electrical force exactly opposes the concentration force — the K⁺ equilibrium potential. A small Na⁺ leak (and the pump) shifts the steady value slightly positive of E_K, to ~−70 mV.

How It Works

1. The Na⁺/K⁺ ATPase establishes high [K⁺] in and high [Na⁺] out.
2. K⁺ leak channels are open at rest; Na⁺ channels are mostly closed.
3. K⁺ diffuses outward, making the inside negative.
4. The growing negative voltage opposes further K⁺ efflux.
5. At equilibrium, K⁺ efflux = K⁺ influx (E_K); with a little Na⁺ leakage, the resting potential settles near −70 mV.

Energy and Directionality

The resting potential is an equilibrium-like steady state, not an energy-consuming one: K⁺ moves passively, and at E_K there is no net K⁺ flux. Energy (ATP) is spent elsewhere — by the Na⁺/K⁺ ATPase — to keep the ion gradients from running down, and by the small Na⁺ leak the pump must continuously counter. Thus the potential itself is "free," but maintaining the gradients that sustain it is costly.

Experimental Evidence

• Changing external K⁺: raising [K⁺]_out shifts the resting potential toward more positive values, closely tracking the Nernst prediction — direct proof that K⁺ permeability sets the potential.
• Ion substitution (removing Na⁺): removing external Na⁺ barely changes the resting potential, confirming Na⁺ contributes little at rest.
• Ouabain blockade: inhibiting the Na⁺/K⁺ ATPase causes the potential to run down slowly (gradients dissipate) rather than collapse instantly — showing the pump maintains gradients rather than generating the potential.
• Single-channel recording: identified the K⁺ leak (K2P) channels responsible for resting K⁺ conductance.

Technique

The resting potential is measured with an intracellular microelectrode or whole-cell patch-clamp; the Nernst and Goldman equations convert measured ion concentrations and permeabilities into the predicted voltage. Varying external ions (especially K⁺) tests the model.

How it works

1. The Na⁺/K⁺ ATPase establishes high [K⁺] in and high [Na⁺] out.
2. K⁺ leak channels are open at rest; Na⁺ channels are mostly closed.
3. K⁺ diffuses outward, making the inside negative.
4. The growing negative voltage opposes further K⁺ efflux.
5. At equilibrium, K⁺ efflux = K⁺ influx (E_K); with a little Na⁺ leakage, the resting potential settles near −70 mV.

Common confusions

• "The Na⁺/K⁺ pump directly produces the resting potential." The pump maintains the ion gradients (and adds only ~a few mV directly); the potential is a K⁺ diffusion potential.
• "The resting potential equals E_K exactly." A small resting Na⁺ permeability (and the pump) shifts it a few millivolts positive of E_K, to ~−70 mV.
• "Na⁺ sets the resting potential." Na⁺ dominates the action-potential upstroke; at rest K⁺ dominates.
• "The cell is at equilibrium." It is a steady state that continuously leaks ions and spends ATP to maintain gradients.

Quick review

• ~−70 mV, inside negative; K⁺-driven diffusion potential.
• K⁺ leak channels + high resting P_K set the value.
• Nernst (one ion) vs. Goldman (weighted multi-ion).
• Pump maintains gradients; K⁺ diffusion generates the voltage.