The Sodium–Potassium Pump: Why You Have a Voltage

Right now, every cell you own is running a tiny electric pump about a hundred times a second, and it is spending roughly a quarter of your resting energy to do it. The Na⁺/K⁺-ATPase throws 3 sodium ions out and drags 2 potassium ions in, burning one ATP each time. Three out, two in — one net positive charge leaves the cell every cycle. That is why the inside of you is negative, why nerves can fire, why your gut can absorb glucose, and why a heart drug made from foxglove works at all. Press Play, then break it five different ways.

Try this: switch to Low magnesium, then press 💉 Give K⁺ and watch the potassium you just gave pour straight back out through the leaky ROMK channel. Now press 💉 Give Mg²⁺ and give the potassium again — this time it stays. That one experiment is why a hospital gives magnesium before it gives potassium.

Diagram is illustrative — not to scale.
OUTSIDE — EXTRACELLULAR FLUID Na⁺ ~145 mM · K⁺ ~4 mM · this is what a blood test measures INSIDE — CYTOSOL Na⁺ ~12 mM · K⁺ ~140 mM · and electrically negative lipid bilayer → +++ +++ +++ −−− −−− −−− ATP site P site P Dx digoxin bound — pump jammed concentration (mM) Na⁺ K⁺ 145 12 4.0 140 if this is a heart cell: force ∝ Ca²⁺ inside dashed = normal cell volume ⚠ CELL SWELLING — water follows Na⁺ in SGLT glucose rides Na⁺ in B⁰AT1 amino acids ride in NCX 3 Na⁺ in → 1 Ca²⁺ out Na⁺/K⁺-ATPase 3 Na⁺ out · 2 K⁺ in · 1 ATP · about 100× a second K⁺ leak (K2P / Kir) K⁺ trickles out ROMK kidney tubule cell this leak — not the pump itself — makes most of the −70 mV net +1 charge leaves per cycle → electrogenic mitochondrion — makes the ATP  

Live cell readout

Membrane potential
−71 mV
0 mV −70 −110
Resting cell ≈ −70 mV. The pump itself supplies only −7 mV of that — the rest comes from K⁺ leaking out.
K⁺ outside (serum)4.0 mM
Normal 3.5–5.0 mmol/L. Dashed line = 3.5.
Na⁺ inside12 mM
K⁺ inside140 mM
100ATP / sec (per pump)
100pump cycles / sec
100Ca²⁺ inside (nM)
100cell volume (%)
ATP burned by this one pump so far: 0
ATP pool5.0 mM
Phosphocreatine buffer25 mM
Phosphocreatine tops ATP back up. It empties first — then ATP falls off a cliff.

What’s happening

The pump is open to the inside, waiting for sodium…
Normal cell. Three Na⁺ out, two K⁺ in, one ATP burned — about 100 times a second.
Na⁺ K⁺ ATP Mg²⁺ phosphate Ca²⁺ glucose amino acid water

What is real and what is a model. The concentrations (Na⁺ ~145 mM outside / ~12 mM inside; K⁺ ~4 mM outside / ~140 mM inside), the 3:2:1 stoichiometry, the resting potential near −70 mV, the pump’s ~20–30% share of a resting cell’s ATP, and the drug mechanisms are all real physiology. The voltage is computed live from a simplified Goldman equation (Na⁺:K⁺ permeability ratio 0.06) plus a −7 mV electrogenic term for the pump; the ion bookkeeping uses a classic pump–leak model with the pump’s real kinetics (Hill coefficient 3 for internal Na⁺, 2 for external K⁺, saturable for ATP and Mg²⁺). The animation runs roughly 300× slower than life so you can see one cycle; the “cycles/sec” readout reports the modelled physiological rate, not the on-screen rate. Absolute Ca²⁺ and cell-volume numbers are illustrative — the directions and the mechanisms are not.

The Science in Plain Language

Why a cell pays a quarter of its energy budget just to be unequal

Left alone, sodium and potassium would mix. Sodium is concentrated outside your cells (about 145 mM) and potassium inside (about 140 mM), and physics wants to flatten that. Every second of your life, sodium leaks in and potassium leaks out, and every second the Na⁺/K⁺-ATPase shoves them back. It is not a lazy background process — it is one of the largest single line-items in your energy budget. In a typical resting cell the pump consumes on the order of 20–30% of all the ATP being made. In the brain, where neurons must reset their charge after every single nerve impulse, the majority of energy use goes to reversing ion movements. That is a big part of why an organ that is about 2% of your body weight burns roughly 20% of your calories at rest.

What do you buy with that enormous, permanent expense? A battery. The steep sodium gradient is stored energy, exactly like water held behind a dam, and nearly everything else in the cell taps it. The Danish physiologist Jens Christian Skou found this enzyme in 1957 while working on crab nerve membranes; forty years later, in 1997, it won him a share of the Nobel Prize in Chemistry. He had discovered the machine that makes you electrical.

Where the −70 mV actually comes from (and the misconception to drop)

Here is the part almost everyone gets slightly wrong. It is true that the pump is electrogenic: three positive charges go out, only two come in, so each cycle exports one net positive charge and makes the inside more negative. But that direct contribution is small — roughly −5 to −10 mV of your resting potential. Block the pump with a drug and the voltage does not instantly collapse; it sags by a few millivolts and then drifts away slowly over minutes as the gradients run down.

The other −60 to −65 mV comes from potassium leaking back out through always-open K⁺ channels (the K2P and Kir families — drawn on the right of the animation). Potassium is 35× more concentrated inside than outside, so it dribbles out down its gradient. Each K⁺ that leaves takes a positive charge with it and leaves its negative partner (proteins, phosphates) behind. The inside goes negative, and that growing negativity starts pulling potassium back in. When push and pull balance, you have the potassium equilibrium potential, given by the Nernst equation: at body temperature, EK = 61.5 mV × log₁₀([K⁺]out / [K⁺]in) = 61.5 × log₁₀(4 / 140) ≈ −95 mV.

Your resting cell sits at about −70 mV rather than −95 mV because the membrane is not perfectly potassium-selective — a small trickle of sodium leaks inward and pulls the voltage back toward positive. So the honest sentence is: the pump does not directly create your voltage; it maintains the potassium gradient, and the potassium gradient creates your voltage. The pump is the generator, the K⁺ leak is the wire. Turn off either and the lights go out — but on very different timescales.

The pump is the battery behind glucose absorption — and behind an entire drug class

Watch the left-hand side of the animation. Three other proteins are quietly spending the sodium gradient the pump built:

  1. SGLT (sodium–glucose linked transporter). Glucose cannot be absorbed uphill on its own. SGLT1 in your small intestine lets sodium fall into the cell — and makes it drag a glucose molecule in with it, against glucose’s own concentration gradient. In the kidney, SGLT2 in the proximal tubule reclaims roughly 90% of the glucose your kidneys filter out, so you do not urinate away your food. Block SGLT2 with a modern diabetes drug (empagliflozin, dapagliflozin, canagliflozin) and you deliberately dump glucose into the urine — a therapy that exists entirely because of the sodium gradient this pump maintains.
  2. Amino-acid transporters (B⁰AT1 and its cousins) do the same trick with amino acids: sodium falls in, and protein building-blocks ride in on its coat-tails.
  3. NCX, the sodium–calcium exchanger. It lets 3 Na⁺ fall inward and uses that energy to heave 1 Ca²⁺ out. Remember this one — it is the whole digoxin story.

The most striking payoff: oral rehydration therapy. Cholera toxin makes the gut pour out salt and water, but it leaves SGLT1 working. Give a dying child water with the right ratio of salt and sugar, and sodium–glucose co-transport pulls sodium across the gut wall, water follows the sodium, and the child rehydrates. A famous 1978 editorial in The Lancet called it “potentially the most important medical advance this century.” It has saved tens of millions of lives — and it works because of the pump you are watching.

Magnesium is the hidden partner — and this is the most useful fact on this page

ATP does not work as ATP. It works as Mg-ATP. The magnesium ion is what neutralises the phosphate charges so the enzyme can grip the molecule and snap the terminal phosphate off. Without magnesium, the cell can be swimming in ATP and the pump still cannot run. Low magnesium is a stalled pump.

It gets worse — and more useful. In the kidney’s collecting duct there is a potassium channel called ROMK. Intracellular magnesium normally sits in its pore like a cork, limiting how much potassium the kidney throws away. When intracellular magnesium falls, the cork comes out: ROMK opens up and the kidney starts wasting potassium into the urine. So a magnesium-deficient person leaks potassium continuously. You can pour potassium into them — orally, intravenously — and it will run straight out again. Hypokalaemia that refuses to correct is hypomagnesaemia until proven otherwise. The fix is to replace the magnesium first (or at the same time); the potassium then stays put. Press Low magnesium in the animation, then Give K⁺, and watch it leave. Then give the magnesium and try again.

And now the trap: a serum magnesium test is a poor way to find this. Only about 1% of your body’s magnesium is in the blood at all — the rest is in bone (roughly half) and inside cells. Serum magnesium is held in a tight range by the kidneys and bone, so it can look perfectly normal while your cells are depleted. A normal magnesium level does not rule out magnesium deficiency. Clinicians who deal with refractory low potassium know this and simply replace magnesium anyway. Adult requirements run about 400–420 mg/day for men and 310–320 mg/day for women, and a large share of adults in Western countries do not reach that from food. Pumpkin seeds, almonds, cashews, spinach, black beans, and dark chocolate are the honest dietary sources.

Potassium is dangerous in both directions — and that is why IV potassium goes in slowly

Serum potassium is normally 3.5–5.0 mmol/L. That narrow window is doing a lot of work: it sets the potassium gradient, and the potassium gradient sets your resting voltage, and your resting voltage decides whether a heart cell fires when it should. Push it out of range in either direction and the heart becomes electrically unstable.

Low (hypokalaemia). Lowering K⁺ outside actually makes the resting potential drift more negative (put K⁺out = 2.5 into the Nernst equation and see for yourself) — but it also slows repolarisation, and that is the danger: a long QT interval, U waves, ectopic beats, and in the worst case torsades de pointes. Muscle weakness, cramps and constipation come along too. Note what happens on screen when you select Low K⁺: the pump reaches the outward-open step and stalls, because it has nothing to bind. Its two potassium sites cannot be filled from a fluid that has run out of potassium.

High (hyperkalaemia). The mirror image, and faster to kill: the resting potential drifts toward zero, sodium channels inactivate, the ECG shows peaked T waves and then a widening QRS, and the heart can arrest. This is precisely why concentrated potassium chloride must never be given as a rapid IV push — it is one of medicine’s classic never-events. Replacement is deliberately unhurried: typically 10 mmol/hour through a peripheral line, going faster (often up to 20 mmol/hour, sometimes more in a crisis) only through a central line with continuous ECG monitoring. When you are refilling a battery this important, you go slowly and you watch the trace.

The digoxin story: a heart drug that works by poisoning this pump — on purpose

Digoxin comes from the woolly foxglove, Digitalis lanata; ouabain, its laboratory cousin, comes from African arrow-poison plants. Both bind the Na⁺/K⁺-ATPase from the outside face — the same face where potassium binds — and jam it. Follow the consequences, because this is one of the most elegant chains in pharmacology:

  1. Pumps are partially blocked → less sodium is exported → intracellular sodium rises.
  2. NCX runs on the sodium gradient. A weaker gradient means NCX cannot heave calcium out as effectively.
  3. Intracellular calcium rises, and more of it gets loaded into the sarcoplasmic reticulum for the next beat.
  4. More calcium per beat = a stronger contraction (positive inotropy). That is literally the therapeutic effect. Select Digoxin in the animation and watch Na⁺ inside climb, the calcium readout climb behind it, and the heart glyph squeeze harder.

The catch is the narrow therapeutic window. For heart failure the target serum level is only about 0.5–0.9 ng/mL; toxicity risk climbs steeply above roughly 2.0 ng/mL, and toxic digoxin causes nausea, confusion, disturbed colour vision (the famous yellow-green haze) and lethal arrhythmias. Two amplifiers make it far more dangerous: low potassium (potassium and digoxin compete for the same site on the pump — less potassium means more digoxin bound, so hypokalaemia turns a therapeutic dose into a toxic one) and declining kidney function, because digoxin is renally cleared. Severe poisoning has a genuine antidote: digoxin immune Fab antibody fragments.

Ischaemia: how the failure of one pump kills a piece of your brain or heart

Cut off the blood supply — a clot in a coronary artery, a clot in a cerebral artery — and oxygen stops arriving. Mitochondria stop making ATP. For a short while phosphocreatine buffers the ATP level, handing over its phosphate to keep ATP topped up (this is the buffer you can watch drain in the animation). Then it runs out, ATP falls off a cliff, and the pump — the biggest ATP consumer in the cell — stops.

Now everything unwinds. Sodium pours in and is not removed. Chloride follows the sodium (charge must balance), and water follows the salt. The cell swells: this is cytotoxic oedema, and in the brain it is the swelling that turns a stroke into a fatal one by raising pressure inside a rigid skull. Meanwhile the collapsing sodium gradient cripples NCX — and if sodium climbs high enough, NCX can run backwards, importing calcium instead of exporting it. Calcium overload then activates the enzymes that digest the cell from within. Select Ischaemia and watch the whole sequence in about thirty seconds: ATP falls, the pump freezes mid-cycle, sodium and water flood in, the cell boundary bulges past its dashed outline, and calcium climbs. This is why “time is brain” and “time is muscle” are not slogans.

What actually raises your potassium (real foods, real amounts)

The adequate intake for adults is about 3,400 mg/day for men and 2,600 mg/day for women, and most people fall well short. Here is the honest ranking — and the banana, that great icon of potassium, is a mid-table player at best:

Two warnings that matter. If you have chronic kidney disease, or you take an ACE inhibitor, ARB, or spironolactone, your ability to excrete potassium is reduced — loading up on potassium (especially via “salt substitutes”, which are largely potassium chloride) can be genuinely dangerous. And if your potassium keeps coming back low despite supplements, re-read the magnesium section above.

Why “electrolyte” drinks are mostly sodium and sugar

A typical 12-ounce sports drink contains roughly 160 mg of sodium, about 45 mg of potassium, and around 21 g of sugar. Read that again: the potassium in a whole bottle is about a tenth of what is in half an avocado, and a twentieth of a baked potato. What you are mostly buying is sodium — which the average Western diet already supplies in excess — plus five teaspoons of sugar. The sugar is not a scam, exactly: glucose genuinely does drive sodium and water absorption through SGLT1 (that is the oral-rehydration trick), which is why these drinks work for an endurance athlete losing litres of sweat, or for someone with gastroenteritis. For someone sitting at a desk, it is a soft drink with a mineral garnish.

If you are actually trying to support the pump, the shopping list is unglamorous and cheap: potassium from plants (potatoes, beans, greens), magnesium from seeds, nuts and legumes, adequate protein, and enough oxygen and calories reaching the tissue to keep the mitochondria making ATP. There is no supplement that makes the Na⁺/K⁺-ATPase run faster than physiology intends — and given what the drugs that do alter it can do to a heart, that is a mercy.

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