Sodium-potassium pump · Grey Matter

The sodium-potassium pump is the membrane enzyme that spends ATP to push sodium out of a cell and potassium in, keeping the two gradients that every neural signal runs on.

Sodium-potassium pump. The sodium-potassium pump is the membrane enzyme that spends ATP to push sodium out of a cell and potassium in, keeping the two gradients that every neural signal runs on.

Each cycle moves three sodium ions out and two potassium ions in for one molecule of ATP. Because more positive charge leaves than enters, the pump adds a small negative contribution to the resting voltage directly, but its main role is slower: it maintains the concentration differences (sodium high outside, potassium high inside) that the channels then discharge in milliseconds. A spike is paid for by the gradient, and the gradient is paid for by the pump.

The pump is the largest single energy cost of the brain. Estimates put it at roughly half of the brain's ATP use, and most of that ATP comes from oxidative phosphorylation, which is why the brain (about 2 % of body mass) takes about 20 % of the body's oxygen at rest.

It keeps up with the running total of activity. One action potential moves only a tiny fraction of the ions in a cell, so the pump answers to the firing rate of the whole tissue; when activity is intense, extracellular potassium rises faster than pumps and astrocytes can clear it.

Its failure spreads. Without ATP the gradients run down, cells depolarise and stop firing; a local, reversible version of the same collapse is what cortical spreading depression looks like, and recovering from it is mostly pump work.

The pump is the battery charger and the channels are the circuit.

Signalling is cheap in the moment and expensive in total, so the brain's energy budget is set by how much charge its signals let through and the pump has to move back.

Questions: Does the sodium-potassium pump power each action potential? Only indirectly. The spike runs on gradients that already exist: voltage-gated channels open and sodium and potassium flow down their concentration differences, with no ATP spent during the event itself. The pump works afterwards and continuously, moving three sodium ions out and two potassium ions in per ATP to restore what the spikes let through. One spike changes the concentrations very little, but the brain fires billions of them, and the bill for restoring the gradients after action potentials and synaptic currents is the largest item in its energy budget. What happens, step by step, when blood stops reaching the brain? Within about 10 seconds consciousness is lost, and within about 20 to 40 seconds the EEG goes flat, because neurons stop firing to conserve energy before ATP has fallen much. Over the next minutes ATP runs out and the sodium-potassium pump stops, so potassium leaks out, sodium, chloride, calcium and water flow in, and the tissue undergoes a sudden, near-total depolarisation (anoxic depolarisation). Terminals then release glutamate that transporters can no longer clear, and calcium overload starts excitotoxic damage. Neurons kept depolarised for more than about half an hour are unlikely to recover even if the circulation returns. 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 the brain use about a fifth of the body's oxygen at about 2 % of its mass? Signalling is paid for by ion gradients, and the gradients are restored by the sodium-potassium pump, which burns ATP made almost entirely by oxidative metabolism. In an adult at rest the brain accounts for about 20 % of the body's oxygen use, around 20 W of a resting total near 100 W. Budgets for rodent cortex attribute most of the signalling cost to pumping ions back after action potentials and after the currents opened by glutamate at synapses, with the resting potential and transmitter recycling costing much less. That is why the brain has almost no energy reserve and fails within seconds to minutes when its blood supply stops.