Regulation of Spermatogenic Cell T-Type Ca2+ Currents by Zn2+: Implications in Male Reproductive Physiology

Zn2+ 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 Zn2+ concentrations, the molecular entities which are modulated by this metal are still under study. Interestingly, spermatogenic cells mainly express Ca(V)3.2-encoded T-type Ca2+ currents (I-CaT) which are positively or negatively modulated by Zn2+ in other tissues. To explore whether I-CaT could be regulated by Zn2+ and albumin, its main physiological carrier, we performed whole cell electrophysiological recordings of spermatogenic cell I-CaT in the absence or presence of different Zn2+ concentrations. Zn2+ decreased I-CaT in a concentration-dependent manner (IC50= 2M) and this inhibition could only be completely removed in presence of albumin. Differently to previous reports, I-CaT did not show a tonic inhibition by Zn2+. Further analysis showed that Zn2+ 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 I-CaT reduction. Using non-stationary fluctuation analysis, we found that Zn2+ mainly reduced the number of available Ca2+ channels without changing the single channel current amplitude. I-CaT modulation by Zn2+ could be relevant for spontaneous Ca2+ oscillations during spermatogenesis and in pathophysiological conditions such as diabetes. J. Cell. Physiol. 231: 659-667, 2016. (c) 2015 Wiley Periodicals, Inc.