Regulation of Spermatogenic Cell T-Type Ca(2+) Currents by Zn(2+): Implications in Male Reproductive Physiology

Zn(2+) is a trace metal which is important for spermatogenesis progression; its deficiency causes atrophy or malignant growth of the testis. Although testis, epididymis, and prostate contain high Zn(2+) concentrations, the molecular entities which are modulated by this metal are still under study. Interestingly, spermatogenic cells mainly express CaV 3.2-encoded T-type Ca(2+) currents (ICaT) which are positively or negatively modulated by Zn(2+) in other tissues. To explore whether ICaT could be regulated by Zn(2+) and albumin, its main physiological carrier, we performed whole cell electrophysiological recordings of spermatogenic cell ICaT in the absence or presence of different Zn(2+) concentrations. Zn(2+) decreased ICaT in a concentration-dependent manner (IC50  = 2 μM) and this inhibition could only be completely removed in presence of albumin. Differently to previous reports, ICaT did not show a tonic inhibition by Zn(2+) . Further analysis showed that Zn(2+) did not affect the voltage dependency or the kinetics of current activation, but right shifted the steady-state inactivation curve and slowed inactivation and deactivation kinetics. Recovery from inactivation was also altered. However, these apparent alterations in gating properties are not enough to explain the strong ICaT reduction. Using non-stationary fluctuation analysis, we found that Zn(2+) mainly reduced the number of available Ca(2+) channels without changing the single channel current amplitude. ICaT modulation by Zn(2+) could be relevant for spontaneous Ca(2+) oscillations during spermatogenesis and in pathophysiological conditions such as diabetes.