Resting membrane potential · Grey Matter

The resting membrane potential is the steady voltage across a neuron's membrane when it is not signalling, about −70 mV with the inside negative, and it is the stored charge every signal spends: inputs move the cell away from it, and a spike is a brief, controlled collapse of it.

Resting membrane potential. The resting membrane potential is the steady voltage across a neuron's membrane when it is not signalling, about −70 mV with the inside negative, and it is the stored charge every signal spends: inputs move the cell away from it, and a spike is a brief, controlled collapse of it.

Two things make it. The sodium-potassium pump keeps potassium about thirty times more concentrated inside than outside (roughly 140 against 5 mM) and sodium more concentrated outside (roughly 140 against 12 mM); chloride and calcium are also far higher outside. At rest the membrane is permeable mostly to potassium, through leak channels that stay open, so potassium drifts out down its gradient and leaves a small excess of negative charge behind. The voltage settles where that outward push is balanced by the electrical pull back, near the potassium equilibrium potential (about −84 mV with those concentrations), pulled a little upward by the small sodium leak.

The number of ions involved is tiny. Charging the membrane takes a thin layer of ions next to it, so the concentrations in the bulk barely change; that is why one spike costs little and why the gradients run down only over many spikes or when the pump stops.

Extracellular potassium is the lever that matters most. Because rest is set by the potassium gradient, a rise of potassium outside (from intense firing, or when astrocytes fall behind) depolarises every neuron nearby at once.

The value varies. Different cells rest between about −60 and −80 mV, and neuromodulators shift it by opening or closing potassium channels.

The resting potential is a battery that the pump charges and the channels discharge.

Every fast event in the brain is a controlled discharge of it, and every slow failure (ischaemia, spreading depression) is the battery running flat.

Questions: Why is the inside of a resting neuron about 70 mV negative? The pump keeps potassium about thirty times more concentrated inside the cell than outside, and at rest the membrane is permeable mostly to potassium through leak channels. Potassium drifts out down its gradient, carrying positive charge with it, until the negative charge left behind pulls back as hard as the gradient pushes; for 140 mM inside and 5 mM outside that balance is near −84 mV. A small leak of sodium inward pulls the real value up to around −70 mV. The pump itself adds only a few millivolts directly (it moves three sodium out for two potassium in); its main contribution is keeping the gradients that the leak then turns into a voltage. Why does a rise of potassium outside the cells make every neuron nearby easier to fire? The resting voltage is set mainly by the potassium gradient, so it depends on the ratio of potassium inside to potassium outside. Outside, potassium is only a few millimolar, so adding a few more millimolar changes that ratio a lot and moves every neuron's resting voltage upward, closer to threshold, all at once. Intense firing releases potassium into the narrow extracellular space faster than pumps can take it back, and astrocytes normally soak it up and spread it through their coupled network. When they fall behind, the extra potassium depolarises the whole neighbourhood, which raises excitability and, at high levels, can start a spreading depolarisation.