Roles of Intracellular Free Zn 2+ on Electrical and Mechanical Activities of the Heart

Zinc is a vital metal in maintaining cellular functions in many cells and Zn 2+ concentration is at the nanomolar range in resting cardiomyocytes. Very little is known about precise mechanisms controlling intracellular free Zn 2+ distribution during cardiac function. To understand role of intracellular Zn 2+ in cardiac physiology, in the present study, we measured simultaneously twitch tension and action potential (AP) in rat ventricular papillary muscles. The amplitude of twitch tension is 25% depressed while rates of both contraction and relaxation are markedly slowed down during a zinc‐ionophore, Zn‐pyrithione (ZnPT, 1 µM). Repolarizing durations at 25, 50, 75, 90% of AP full repolarization are significantly prolonged during this exposure. The whole‐cell voltage‐clamp technique was applied to isolated ventricular myocytes to investigate the effects of ZnPT exposures on L‐type Ca 2+ channel currents (I CaL ). In presence of Ca 2+ , Zn 2+ exposures demonstrated strong inhibitory effects on I CaL with significant alteration in voltage dependency of the channels and a hump at around ‐40 mV in the current‐voltage relationship. Additionally, our preliminary data indicated that intracellular free Zn 2+ could inhibite a steady‐state K(+) current which modulates excitability and AP duration in cardiomyocytes. Therefore, our results suggested that an intracellular Zn 2+ increase can induce depressed electrical and mechanical activity of cardiac preparations, in most, its modulatory action on transmembrane Ca 2+ movements. Of note, in many pathological situations, including diabetes, the intracellular Zn 2+ is increased, our results help to explain one of underlying mechanisms associated with cardiac dysfunction in these diseases. ( Supported by grant from TUBITAK SBAG‐113S466 )