Regulation and interaction of intracellular calcium, sodium and hydrogen ions in cardiac muscle.

The contractility of heart muscle is sensitive to the relative cytoplasmic concentrations of Na+, H+ and Ca++. The concentration of Na+ is mainly controlled by the Na+/K(+)-ATPase while the concentration of H+ is regulated by the Na+/H+ and Cl-/HCO3- exchanges. Cytoplasmic Ca++ concentration is mainly under the control of the sarcolemmal Na+/Ca++ exchange and Ca(++)-ATPase and sarcoplasmic reticular Ca(++)-ATPase. However, in heart muscle there is also a complex interaction between these ions such that altering the main regulation of one will affect the intracellular levels of the other two. Such interaction may thus enhance or attenuate the contractile response to the initial change. This review briefly describes the properties of the main regulatory mechanisms and focuses on their interactions and what consequences these have for contraction.