Potassium is the primary intracellular cation in the human body — it is present at concentrations of approximately 150mEq/L inside the cells and at approximately 4-5mEq/L in the blood and the extracellular fluid, and this 30-40-fold concentration gradient across the cell membrane is the primary determinant of the resting membrane potential in all excitable cells (neurons, muscle cells, cardiac myocytes). The resting membrane potential is established by the selective permeability of the cell membrane to the potassium ions — the membrane is permeable to the potassium (through the potassium leak channels, which are open at rest), but it is relatively impermeable to the other ions (sodium, chloride, calcium). The potassium ions flow down their concentration gradient from the inside to the outside of the cell, creating the negative charge inside the cell (the resting membrane potential, which is approximately -70mV in most excitable cells). This resting membrane potential is essential for the excitability of the neurons and the muscle cells — it is the electrical baseline from which the action potentials are generated when the cell is stimulated. Without adequate potassium and this concentration gradient, the resting membrane potential is depolarised (becomes less negative), the cell excitability is impaired, and the muscle weakness, the cardiac arrhythmias, and the paralysis develop — the hallmark of the hypokalaemia. The typical dietary potassium intake is 2-4g daily (from the fruits, the vegetables, the legumes, and the potatoes), and the adequate intake is 3.4g daily for men and 2.6g daily for women — but the potassium deficiency is extremely common (affecting 50-80% of the population in the developed world), because the modern diet is low in potassium (due to the processing of the foods and the removal of the potassium-rich fruits and vegetables) and because the common medications (diuretics, laxatives, corticosteroids) increase the urinary or the gastrointestinal potassium loss.
Potassium and the Action Potential
The action potential is the brief, rapid reversal of the membrane potential that is used for the communication in the nervous system and for the contraction in the muscle cells — it is initiated by the depolarisation of the membrane potential (which opens the voltage-gated sodium channels, causing the rapid influx of sodium and the further depolarisation) and is terminated by the repolarisation (which opens the voltage-gated potassium channels, causing the efflux of potassium and the restoration of the resting membrane potential). The potassium channels are therefore essential for the repolarisation phase of the action potential — without adequate potassium and functional potassium channels, the repolarisation is slowed or prevented, the action potential is prolonged, and the cell excitability is dysregulated. This potassium-dependent dysregulation of the action potential is the primary mechanism of the cardiac arrhythmias, the muscle weakness, and the paralysis that are associated with the hypokalaemia.
The clinical importance of the potassium for the cardiac excitability is underscored by the observation that the hypokalaemia (blood potassium below 3.5mEq/L) is one of the most common and most dangerous electrolyte disturbances — it is associated with the cardiac arrhythmias (including the atrial fibrillation, the ventricular tachycardia, and the torsades de pointes), with the muscle weakness, with the constipation, and with the paralysis. A study in 1000 patients with the heart failure found that the hypokalaemia was associated with a 3-fold increased risk of the all-cause mortality and a 5-fold increased risk of the sudden cardiac death compared to the normal serum potassium — demonstrating the critical importance of the potassium for the cardiac function.
Practical Application
For general potassium supplementation, the evidence-based approach is to supplement with 1-3g of potassium daily (as potassium citrate, potassium chloride, or potassium bicarbonate — the forms that are well absorbed and well tolerated). The potassium citrate form is preferred for the people with the metabolic acidosis (because it is metabolised to the bicarbonate and can help to correct the acidosis), and the potassium chloride form is preferred for the people with the chloride deficiency or the metabolic alkalosis. The potassium should be taken with food and should be titrated gradually to the therapeutic dose (to reduce the gastrointestinal side effects and to avoid the hyperkalaemia). The adequate intake of potassium is 3.4g daily for men and 2.6g daily for women, and the tolerable upper intake level is not established (because the high-dose potassium supplements can cause the hyperkalaemia, which is a medical emergency that requires immediate treatment). For comprehensive cardiovascular and neuromuscular support, potassium pairs well with the magnesium (which is a natural potassium channel blocker and which works synergistically with potassium for the maintenance of the resting membrane potential and for the prevention of the cardiac arrhythmias), with the sodium (which is the primary extracellular cation and which works with potassium to maintain the blood pressure and the fluid balance), with the calcium (which is the primary regulator of the muscle contraction and which is antagonised by the potassium deficiency), and with the vitamin D (which has cardiovascular protective effects and which is increasingly recognised as an important determinant of the blood pressure and of the cardiovascular risk).
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