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

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.