Inhibition of late (sustained/persistent) sodium current: a potential drug target to reduce intracellular sodium-dependent calcium overload and its detrimental effects on cardiomyocyte function

Abstract

This article describes a potential target for therapeutic intervention in ischaemia and heart failure – inhibition of the late (sustained) sodium current to reduce the rise in intracellular sodium and calcium, and to reduce the electrical and mechanical abnormalities associated with these conditions. The new anti-anginal and antiischaemic drug ranolazine is a selective inhibitor of the late sodium current that is capable of reducing the electrical instability and mechanical dysfunction associated with conditions (e.g. ischaemia, heart failure) known to raise late INa and [Na+]i. Because the scope of the review is narrow, many relevant mechanisms involved in the regulation of intracellular sodium and calcium homeostasis are not discussed, and important individual contributions are not cited. Hence, the reader is referred to more comprehensive reviews of this subject.