Potassium is the primary intracellular cation in the human body — it is present at concentrations of approximately 150mM inside the cells and at approximately 4mM in the extracellular fluid, and this 35-fold concentration gradient across the cell membrane is the foundation of the resting membrane potential that is essential for the function of all electrically excitable cells, including the neurons, the muscle cells (including the cardiac muscle), and the endocrine cells. The maintenance of this potassium gradient is achieved by the Na+/K+ ATPase — the sodium-potassium pump that is embedded in the cell membrane and that uses the energy of ATP hydrolysis to pump three sodium ions out of the cell and two potassium ions into the cell for every cycle of the pump. This active transport of sodium and potassium by the Na+/K+ ATPase maintains the ionic gradient that is essential for the resting membrane potential, for the action potential generation, for the nerve impulse conduction, for the muscle contraction, and for the endocrine secretion — and when the potassium levels in the blood are low (hypokalaemia), the intracellular potassium concentration falls, the resting membrane potential is altered, and the function of all electrically excitable cells is impaired.
The Sodium-Potassium Pump and the Resting Membrane Potential
The resting membrane potential is the electrical potential difference that exists across the cell membrane of all cells at rest — it is typically -70mV in neurons and in muscle cells (meaning that the inside of the cell is 70mV more negative than the outside), and it is established by the differential permeability of the cell membrane to different ions. At rest, the cell membrane is much more permeable to potassium than to sodium — the potassium channels (particularly the inward rectifier potassium channels) allow potassium to flow out of the cell down its concentration gradient, leaving behind the negatively charged intracellular proteins and creating the negative intracellular potential. The Na+/K+ ATPase maintains this gradient by continuously pumping potassium into the cell and sodium out of the cell, counteracting the small amount of potassium and sodium leakage that occurs through the membrane channels. When the extracellular potassium concentration is low (hypokalaemia), the driving force for potassium efflux through the potassium channels is reduced, the membrane potential is hyperpolarised (more negative), and the excitability of the cell is reduced — this is the mechanism of the muscle weakness, the fatigue, and the reduced nerve conduction velocity that are the clinical manifestations of hypokalaemia.
The clinical importance of potassium for the cardiac function is underscored by the observation that hypokalaemia is one of the most common causes of cardiac arrhythmias — including the ventricular tachycardia, the ventricular fibrillation, and the torsades de pointes (the polymorphic ventricular tachycardia that is associated with the prolonged QT interval). The cardiac myocytes are particularly sensitive to potassium levels because the resting membrane potential and the action potential duration are critically dependent on the intracellular potassium concentration, and when the potassium concentration falls, the cardiac myocytes become more excitable (more likely to fire an action potential) and more prone to the arrhythmias that are triggered by the early afterdepolarisations (EADs) and the delayed afterdepolarisations (DADs) that are the initiating events in the ventricular tachycardia and fibrillation. The correction of hypokalaemia is therefore one of the most urgent therapeutic priorities in the management of cardiac arrhythmias.
Potassium and Blood Pressure Regulation
Potassium also plays an important role in the regulation of the blood pressure — it is an antagonist of the sodium in the regulation of the extracellular fluid volume and of the vascular tone, and the high potassium intake that is characteristic of the DASH dietary pattern (which is the most effective non-pharmacological intervention for the reduction of the blood pressure) is one of the primary mechanisms of the blood pressure reduction that is achieved by this dietary approach. The mechanism by which potassium reduces the blood pressure involves the increased renal excretion of sodium (potassium is natriuretic — it promotes the excretion of sodium in the urine), the reduced vascular tone (potassium causes vasodilation by opening the potassium channels in the vascular smooth muscle cells, which causes the membrane to hyperpolarise and reduces the calcium influx through the voltage-gated calcium channels), and the reduced sensitivity of the vascular smooth muscle to the vasoconstrictor hormones (including angiotensin II and norepinephrine). These effects of potassium on the blood pressure are complementary and together they produce the significant blood pressure reduction that is observed in the high-potassium dietary patterns.
Practical Application
For general potassium supplementation, the evidence-based approach is to consume 3,500-4,700mg of potassium daily from food sources (bananas, avocados, spinach, sweet potatoes, beans, yoghurt), which is approximately the RDA of 4,700mg daily for adults. For the treatment of hypokalaemia, potassium supplementation at 20-40mEq/L of KCl (equivalent to approximately 750-1,500mg of elemental potassium) is administered intravenously in the acute hospital setting, and oral potassium supplementation at 20-40mEq daily (equivalent to approximately 750-1,500mg of elemental potassium) is used in the outpatient setting. Potassium chloride is the most commonly used supplemental form because it is the form that is most rapidly absorbed and because it is the form that is used in the treatment of hypokalaemia. For comprehensive electrolyte and cardiovascular support, potassium pairs well with magnesium (which is the intracellular cation that is most closely related to potassium in terms of its physiological functions and whose deficiency can mimic hypokalaemia), with sodium (which is the extracellular cation that is antagonistic to potassium in terms of its effects on the fluid balance and on the blood pressure), and with the DASH dietary pattern (which is the most evidence-based dietary approach for the reduction of the blood pressure).
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