Zinc-induced changes in ionic currents of cardiomyocytes

The whole-cell voltage-clamp technique was applied to isolated ventricular myocytes to investigate the effects of extracellular and intracellular zinc application on L-type Ca2+ channel currents (I-Ca). Extracellular zinc exposure at micromolar concentration induced a reversible (with washout of ZnCl2) reduction (30%) of I-Ca with no change in current-voltage relationship. On the other hand, an increase of intracellular free-zinc concentration, [Zn2+](i), from normal (less than 1 nM) to approx 7 nM with 10 muM Zn-pyrithione exposure caused an inhibition of 33+/-6% in the peak of the I-Ca and altered the voltage dependency of L-type Ca2+ channels with a 10-mV left shift and a hump at around -40 mV in its current-voltage relation. In contrast, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly inhibited the I-Ca (42+/-2%), with only a small but detectable outward shift of the holding current measured at the end of the pulses. Zn-pyrithione and TPEN caused a reproducible decrease of the I-Ca. Interestingly, TPEN application, without Zn-pyrithione pretreatment, inhibited the I-Ca (35+/-2%) with no change in voltage dependency. Taken together, the results suggest that both extracellular and intracellular zinc increases under pathological conditions in cardiomyocytes can alter the I-Ca, but their effects are not in the same order and same manner. One should consider these possible side effects when it is suggested to be vital to cardiovascular cell integrity and functions.