Resting Membrane Potential

What the resting potential actually is

Stick a microelectrode through the membrane of a quiet neuron and you read a voltage: the inside sits roughly 70 millivolts more negative than the fluid outside. That number, the resting membrane potential, is not an accident or a leftover — it is an actively defended steady state, a charged battery the cell keeps topped up so it can do electrical work the instant it needs to.

The voltage seems large for a living cell, but the membrane is only about 4 nanometers thick. A −70 mV drop across 4 nm is an electric field of roughly 17 million volts per meter — strong enough to reorient the proteins embedded in the membrane and to slam ion channels open or shut. The cell is, in effect, a microscopic capacitor whose two plates are the salty fluids on either side of an insulating lipid sheet.

Crucially, only a tiny amount of charge has to move to set up this voltage. The membrane's capacitance is about 1 microfarad per square centimeter. To charge it to −70 mV takes on the order of 10−¹² moles of ions per square centimeter — a layer of unbalanced charge so thin that the bulk concentrations of K+, Na+, and Cl− inside and outside the cell barely budge. The cytoplasm and extracellular fluid remain almost perfectly electroneutral; the imbalance lives in a vanishingly thin skin pressed against the inner and outer faces of the membrane.

The mechanism: a potassium battery

Two ingredients build the resting potential: ion concentration gradients and selective permeability. Neither alone is enough. Gradients without open channels produce no current; channels without gradients have nothing to drive.

At rest, the membrane is dotted with potassium leak channels (in many cells, two-pore-domain K2P channels and inward-rectifier Kir channels) that stay open and let K+ pass freely. Sodium leak is far smaller. The membrane is therefore something like 25 to 100 times more permeable to K+ than to Na+.

Potassium is concentrated inside the cell — about 140 mM in versus 5 mM out. That steep chemical gradient pushes K+ outward through the leak channels. But every K+ ion that leaves carries a positive charge with it, and the large intracellular anions it leaves behind — proteins, organic phosphates, nucleic acids — cannot follow through the membrane. So the interior loses positive charge and grows negative.

That negativity is itself a force: a negative interior electrically attracts the positive K+ back inward. As more K+ leaks out, the negativity deepens, the inward electrical pull strengthens, and outward K+ flow slows. Equilibrium arrives when the outward chemical push exactly equals the inward electrical pull. At that voltage — the equilibrium potential for potassium — net K+ flow is zero even though individual ions still cross both ways.

Putting numbers on it: Nernst and Goldman

The Nernst equation calculates that equilibrium potential for a single ion. At body temperature (37 °C) for a singly charged ion it reduces to a clean form:

E_ion = 61.5 mV × log₁₀([ion]_out / [ion]_in)

Plug in the gradients and you get the equilibrium potential each ion is "trying" to drag the membrane toward:

Ion	Inside (mM)	Outside (mM)	Equilibrium potential (37 °C)	Resting permeability
K+ (potassium)	~140	~5	≈ −90 mV	High (leak channels open)
Na+ (sodium)	~15	~145	≈ +60 mV	Very low
Cl− (chloride)	~10	~110	≈ −65 mV	Moderate (cell-dependent)
Ca²+ (calcium)	~0.0001	~1.2	≈ +120 mV	Negligible at rest

If the membrane were permeable to K+ alone, the resting potential would sit right at E_K ≈ −90 mV. But it is not perfectly selective. A small Na+ leak constantly trickles inward, dragging the voltage a little positive, away from E_K and toward E_Na. That is why a real neuron rests near −70 mV rather than −90 mV.

The Goldman–Hodgkin–Katz (GHK) equation captures this tug-of-war by weighting each ion's equilibrium potential by its permeability. The membrane voltage is a permeability-weighted average of the individual equilibrium potentials: whichever ion the membrane is most permeable to wins the largest vote. At rest, K+ dominates, so the resting potential lands close to E_K; during an action potential, Na+ permeability briefly explodes a thousandfold and the voltage lurches toward E_Na.

The Na/K pump: rebuilding the gradients

The leak channels would, left alone, slowly bleed the gradients flat — K+ would seep out, Na+ would seep in, and the battery would discharge. The sodium-potassium pump (Na+/K+-ATPase) prevents that. Burning one molecule of ATP, it ejects 3 Na+ and imports 2 K+ against their gradients. A single neuron may carry millions of these pumps, and in some cells the Na+/K+-ATPase consumes 20 to 70 percent of the cell's resting ATP budget — a substantial energy bill paid purely to keep the battery charged.

The pump's primary role is indirect: it maintains the concentration gradients that the leak channels exploit. The gradients, not the pump's instantaneous current, are the true source of the voltage. But the pump also contributes directly. Because it moves three positive charges out for every two it brings in, each cycle nets one positive charge leaving the cell. This makes the pump electrogenic, adding a small extra negativity — typically −2 to −10 mV — on top of the diffusion potential. Poison the pump with ouabain or starve it of ATP and the resting potential does not collapse instantly; it decays over minutes to hours as the gradients slowly run down.

Contributor	Role at rest	Effect on voltage
K+ leak channels	Let K+ diffuse out down its gradient	Drives voltage toward EK (≈ −90 mV) — dominant
Na+ leak	Small inward Na+ trickle	Pulls voltage positive, toward −70 mV
Na+/K+-ATPase (gradients)	Restores K+ in, Na+ out	Indirect — sustains the gradients that make the voltage possible
Na+/K+-ATPase (electrogenic)	Net 1+ charge exported per cycle	Direct − a few extra mV of negativity
Impermeant intracellular anions	Trapped proteins, phosphates	Provide the fixed negative charge K+ leaves behind

Different cells, different batteries

The resting potential is not a universal constant; cells tune it to their job. Neurons rest near −70 mV. Skeletal muscle fibers, packed with K+ channels and a high chloride permeability, sit deeper at about −90 mV. Cardiac pacemaker cells in the sinoatrial node refuse to hold a stable rest at all — their leak currents and "funny" channels make the voltage drift steadily upward toward threshold, generating a heartbeat every drift cycle, roughly once a second. Smooth muscle and many secretory cells rest shallower, around −40 to −60 mV, closer to their excitable threshold.

Even non-excitable cells maintain a resting potential. Plant cells, fungi, and bacteria all hold a membrane voltage, though plants and many microbes use a proton gradient and an H+-ATPase rather than the animal Na+/K+ scheme. Red blood cells, which never fire, still keep a modest potential to control their ion content and volume. The principle is ancient and near-universal: any cell that wants to do osmotic work, transport nutrients, or signal must first separate charge across its membrane.

Clinical and evolutionary significance

Because the resting potential tracks E_K, it is exquisitely sensitive to blood potassium. Raise extracellular K+ (hyperkalemia) and the K+ gradient shrinks, E_K climbs, and cells depolarize toward threshold. In the heart this can trigger fatal arrhythmia — which is exactly why potassium chloride is a component of lethal injection and why dialysis patients are monitored so closely. Lower extracellular K+ (hypokalemia) and cells hyperpolarize, becoming sluggish and hard to excite, causing muscle weakness. The body therefore guards plasma K+ within a tight 3.5–5.0 mM window.

The deeper significance is energetic and informational. By pre-charging a battery and holding it just shy of threshold, a cell stores potential energy it can release in under a millisecond. The action potential does not have to manufacture its driving force on demand; it merely opens a gate and lets the pre-built gradient pour ions through. Evolution discovered that maintaining a standing voltage — paying a continuous ATP tax — buys an enormous gain in response speed. Nervous systems, fast muscle, and rapid secretion all depend on this trick. The resting membrane potential is the quiet, expensive readiness that makes the body's electricity possible.

Common misconceptions

• "The pump directly makes the voltage." Mostly no — the pump builds the gradients; the leak of K+ down those gradients makes the voltage. The pump's direct electrogenic share is only a few mV.
• "Equal numbers of ions are inside and out." Concentrations differ enormously; it is the charge balance, slightly broken at the membrane, that sets the voltage.
• "Lots of ions move to set −70 mV." Only a microscopically thin layer of charge separates; bulk concentrations barely change.
• "Resting potential equals E_K." It sits near E_K but is pulled positive by the small Na+ leak, landing around −70 mV.
• "The membrane is at equilibrium." It is a steady state, not equilibrium — the pump continuously spends ATP to hold it.