The role of Zn(2+) in shaping intracellular Ca(2+) dynamics in the heart

Increasing evidence suggests that Zn(2+) acts as a second messenger capable of transducing extracellular stimuli into intracellular signaling events. The importance of Zn(2+) as a signaling molecule in cardiovascular functioning is gaining traction. In the heart, Zn(2+) plays important roles in excitation–contraction (EC) coupling, excitation–transcription coupling, and cardiac ventricular morphogenesis. Zn(2+) homeostasis in cardiac tissue is tightly regulated through the action of a combination of transporters, buffers, and sensors. Zn(2+) mishandling is a common feature of various cardiovascular diseases. However, the precise mechanisms controlling the intracellular distribution of Zn(2+) 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 Zn(2+) is regulated in the heart, the role of Zn(2+) in EC coupling, and discuss how Zn(2+) dyshomeostasis resulting from altered expression levels and efficacy of Zn(2+) regulatory proteins are key drivers in the progression of cardiac dysfunction.