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

• Published in: Journal of cellular physiology Vol. 231; no. 3; pp. 659 - 667
• Main Authors: López-González, Ignacio, Treviño, Claudia L., Darszon, Alberto
• Format: Journal Article
• Language: English
• Published: Hoboken Blackwell Publishing Ltd 01.03.2016; Wiley Subscription Services, Inc
• Subjects: Inactivation; Kinetics; Physiology; Trace metals
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.25112

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 CaV3.2‐encoded T‐type Ca2+ currents (ICaT) which are positively or negatively modulated by Zn2+ in other tissues. To explore whether ICaT could be regulated by Zn2+ and albumin, its main physiological carrier, we performed whole cell electrophysiological recordings of spermatogenic cell ICaT in the absence or presence of different Zn2+ concentrations. Zn2+ 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 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 ICaT 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. ICaT 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. © 2015 Wiley Periodicals, Inc.