Serum potassium, hydrogen ion and magnesium: neuromuscular regulation by variation of cation concentration in the extracellular fluid?

It is a common clinical observation that changes in serum [K] are frequently associated with changes in serum [H] and/or [Mg]. Thus, hypokalaemia and alkalosis are associated, as are hyperkalaemia and acidosis, and hypokalaemia and hypomagnesaemia. Most investigators would accept that these ions have important roles in the maintenance of neuromuscular excitability. Extracellular potassium exerts its effect by defining the potassium gradient across the cell membrane and therefore the membrane potential in the resting state; magnesium and hydrogen ion 'screen' negative charges on the surface of nerve cells, modulating the local transmembrane potential gradient, to which the voltage-sensitive channels governing the initiation of the action potential respond. It is pointed out here that the changes in ionic concentration observed in pathophysiology are not incompatible with the idea that the associated changes reflect regulatory events in the extracellular fluid designed to preserve excitability.