TRPC6-mediated Zn2+ Influx as a Cardiotonic Mediator

Zinc ions (Zn2+) are one of the essential and most abundant micronutrients in the human body. Zn2+ bind to intracellular biomolecules, regulating various functions such as enzyme activity, signal transduction, and gene expression. A deficiency of Zn2+ can lead to various pathological conditions and diseases. It is believed that intracellular Zn2+ homeostasis is precisely regulated by the uptake and excretion of Zn2+via transporters and carriers. However, little research has been conducted on the mechanisms that control changes in Zn2+ dynamics and the resulting biological functions caused by physicochemical environmental stress. We have recently discovered that intracellular Zn2+ plays a crucial role in the enhancement of myocardial contractility via the baroreceptor reflex and that the molecular entity responsible for Zn2+ influx from the extracellular space during sympathetic stimulation is the receptor-operated transient receptor potential (TRP) channel, TRPC6. In this chapter, we focus on Zn2+-permeable TRP channels responsive to environmental stress and provide an overview of their pathophysiological roles, especially in hearts.