This long read begins with the measured value: where does the negative voltage of a resting fiber come from, how much of it can be reproduced on paper with rounded concentrations, and in which order do the pump and the channels go to work when a signal comes in?
An adult carries somewhere around 120 to 140 grams of potassium, the exact figure depending on how much muscle tissue the person has. Very little of it is in the blood; nearly all of it is held inside cells. Skeletal muscle makes up the largest reservoir, simply because it accounts for the largest share of the body’s cell mass.
The table below lists rounded guide values for a skeletal muscle fiber and the fluid that surrounds it. Some textbooks give slightly different figures, but the order of magnitude matches from one source to the next.
| Ion | Inside the fiber (mmol/L) | Between the cells (mmol/L) |
|---|---|---|
| Potassium (K+) | approx. 150–155 | approx. 4–5 |
| Sodium (Na+) | approx. 12 | approx. 145 |
| Chloride (Cl−) | approx. 4 | approx. 120 |
For potassium, that puts the inside-to-outside ratio at about thirty to one. This very ratio is what the next section turns into a voltage.
Picture a membrane that lets nothing but potassium through. Potassium ions would drift outward until the negative charge they leave behind pulls them back in exactly as hard as the gradient pushes them out. The voltage at which that standoff is reached is called the equilibrium potential.
At body temperature, the equilibrium potential of an ion with a single charge can be written in a simplified way: the voltage in millivolts equals 61.5 multiplied by the base-10 logarithm of the outside concentration divided by the inside concentration.
61.5 × log (4.5 ÷ 155) ≈ 61.5 × (−1.54) ≈ −95 mV
At a resting fiber, the reading comes out at about minus 85 to minus 90 millivolts. So the measured value sits close to the calculated potassium figure without quite getting there.
The membrane is not fully sealed against other ions. A small inflow of sodium nudges the voltage part of the way toward zero. Skeletal muscle fibers add a feature of their own: much of their conductance at rest runs through chloride channels of the ClC-1 type. Chloride distributes itself largely passively in line with the voltage, so it behaves like a buffer that smooths out brief fluctuations.
Even so, the potassium gradient is still what fixes where the resting voltage lies. If the potassium concentration outside the cell moves, that starting value moves with it.
Left without resupply, any fiber would gradually lose its gradient, since a little potassium is always leaking out through open channels and a little sodium leaking in. The pump makes good that loss. While doing so it switches between two basic positions, which biochemistry labels E1 and E2.
| Phase | What takes place at the pump |
|---|---|
| E1, open toward the inside | Three sodium ions attach on the inner face, and ATP docks. |
| Phosphorylation | A phosphate group is handed over to the alpha subunit, and the sodium ions are shut in. |
| E2, open toward the outside | The pump tips over and lets the sodium go on the outer face. |
| Potassium binding | Two potassium ions take the sites that have just been freed, and the phosphate group comes off. |
| Back to E1 | The pump tips back and lets the potassium go into the cell interior. |
In each round, three positive charges leave the cell and two come in. That makes the pump electrogenic: it produces a small current of its own and shifts the cell interior a few millivolts further into the negative. The bigger share of its effect on the resting voltage, though, is indirect and runs through the potassium gradient it creates.
In humans, the alpha subunit exists in four versions. Skeletal muscle is dominated by the alpha-2 version, with alpha-1 present alongside it. Some of the pumps sit in the surface membrane, others in the T-tubules, slender infoldings that run deep into the fiber. Hormones such as insulin can step up the pump’s activity and in this way move more potassium into the cells.
At the motor end plate, a chemical signal is converted into a local change in membrane voltage. When that change crosses a threshold, an action potential arises and travels along the whole fiber. In a skeletal muscle fiber it is over within a few milliseconds.
Voltage-gated sodium channels open first. Sodium flows in, and for an instant the cell interior becomes positive. Almost at once, those sodium channels start to shut again. After a short delay, voltage-gated potassium channels open, potassium flows out, and the voltage drops back into the negative range. Until the sodium channels are ready once more, the fiber stays unresponsive to a new signal for a brief moment.
The action potential also travels down into the T-tubules. Voltage sensors located there are coupled to the calcium stores inside the fiber and in this way set off the shortening of the fiber proteins. Because the T-tubules are so narrow, potassium that has flowed out can briefly collect there when signals follow one another quickly. The sodium-potassium ATPase in the tubule membrane takes it back in.
The list of authorized health claims includes a wording on muscle function for potassium. It reads as follows:
“Potassium contributes to normal muscle function”
EU-authorized wording · Regulation (EU) No 432/2012“Normal” refers here to the ordinary day-to-day working of a muscle fiber whose potassium needs are covered. The sentence says nothing that goes past that ordinary state.
Because the resting voltage hinges so directly on the ratio between inside and outside, the body holds the potassium concentration in blood plasma inside a tight window of about 3.5 to 5 millimoles per liter.
Over longer periods, the kidneys decide how much potassium leaves the body. The hormone aldosterone raises excretion when the concentration goes up. This is how the potassium taken in with food each day is evened out over a span of hours to days.
After a meal, potassium reaches the blood faster than the kidneys can clear it. During that window, muscle and liver cells above all take up part of it for a while, driven by pumps whose activity insulin raises. In this role, skeletal muscle also acts as an interim store.
For nutrition labeling on foods, Regulation (EU) No 1169/2011 sets an EU reference intake for potassium of 2,000 mg per day. In 2016, the European Food Safety Authority (EFSA) derived an adequate intake of 3,500 mg per day for adults. The two figures serve different purposes, and neither is meant as a personal recommendation.
No. The fiber works within a range where the gradient is right. If the outside level sits clearly above or below that range, the resting voltage shifts in an unfavorable way, whichever direction it goes. The authorized claim refers explicitly to normal function.
Only up to a point. The plasma value reflects the small share outside the cells, which is kept within close limits. How much is stored inside the cells cannot be read off it directly. Making sense of a lab result is a job for a doctor.
Potassium occurs in many plant foods, for instance potatoes, legumes, leafy greens, nuts and dried fruit, and also in dairy products and fish. This long read keeps its focus on purpose on the mechanism at the membrane rather than on meal plans.
The EU has authorized more than one wording for potassium. The topic of this site is the muscle fiber alone, so it quotes only the wording that belongs to that topic.
The calculation, the pump cycle, the signal sequence and the follow-up questions in one self-contained edition that you can read free of ads and without a network connection.
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