The role of Zn2+ in shaping intracellular Ca2+ dynamics in the heart

Abstract

Increasing evidence suggests that Zn2+ acts as a second messenger capable of transducing extracellular stimuli into intracellular signalling events. The importance of Zn2+ as a signalling molecule in cardiovascular functioning is gaining traction. In the heart, Zn2+ plays important roles in excitation-contraction (EC) coupling, excitation-transcription coupling, and cardiac ventricular morphogenesis. Zn2+ homeostasis in cardiac tissue is tightly regulated through the action of a combination of transporters, buffers and sensors. Zn2+-mishandling is a common feature of various cardiovascular diseases. However, the precise mechanisms controlling the intracellular distribution of Zn2+ and its variations during normal cardiac function and during pathological conditions are not fully understood. In this review we consider the major pathways by which the concentration of intracellular Zn2+ is regulated in the heart, the role of Zn2+ in EC coupling and discuss how Zn2+-dyshomeostasis resulting from altered expression levels and efficacy of Zn2+ regulatory proteins are key drivers in the progression of cardiac dysfunction.