Fig. 2

Transporters and channels involved in the handling of protons, sodium, calcium and potassium in myocytes. At normal sodium concentrations the NCX of the sarcolemma works in the forward mode to export calcium. At high sodium concentrations caused by high NHE1- and low Na⁺/K⁺-ATPase activity the NCX reverses its transport direction to import calcium leading to calcium overload. Since intracellular sodium is the driving force for the mitochondrial NCX, elevated intracellular sodium (even below the threshold for reverse mode of the sarcolemmal NCX) activates the mitochondrial NCX to diminish mitochondrial calcium while elevated cytoplasmatic calcium has the opposing effect and tends to increase it. KATP is closed at normal but activated at low ATP levels. Opening will cause hyperpolarization, a protective mechanism against calcium overload. But if open for a longer time it can cause potassium loss together with the weak Na⁺/K⁺-ATPase activity, for which the causes are listed in Table 1. Intracellular hypokalemia reduces the driving force of the protective KATP opening