Voltage-operated calcium channels in male germ cells

Abstract

Sexual reproduction in mammals is achieved by the fusion of a spermatozoon with the oocyte. The spermatozoon must penetrate the egg vestments and bind to the oolemma before gamete fusion can occur. A pivotal event in this process is the acrosome reaction wherein the acrosome, a secretory vesicle in the apical region of the spermatozoon, fuses with the overlying plasma membrane. This fusion results in secretion of the acrosomal contents and also incorporation of the inner acrosomal membrane into the plasmalemma. These processes are believed to be important for penetration of the zona pellucida and sperm-oocyte fusion (Ward and Kopf, 1993). Agonist-induced Ca 2+ signalling in spermatozoa and male infertilityAcrosome reaction is a secretory event triggered as the spermatozoon approaches the egg (Yanagimachi, 1994). Although a number of intracellular messenger systems have been implicated and the biochemistry of the acrosome reaction is complex (Ward and Kopf, 1993;Breitbart and Spungin, 1997), it appears that gating of Ca 2+ channels and consequent Ca 2+ influx plays a central role. In several mammals, a sustained increase in [Ca 2+ ] i , dependent upon influx of extracellular Ca 2+ , is induced directly by solubilized zona pellucida. The initial phase of zona pellucida-induced Ca 2+ influx appears to require activation of voltage-operated calcium channels (VOCCs). Organic and inorganic antagonists of VOCCs, including 1,4-dihydropyridines (DHPs), a class of drugs specific for these channels, inhibit both the zona pellucida-induced Ca 2+ signal and the consequent acrosome reaction (Florman et al., 1998;Darszon et al., 1999;Publicover and Barratt, 1999). Progesterone is the only other well-characterized agonist of the acrosome reaction. In a similar manner to the zona pellucida, progesterone causes a rapid and transient increase in [Ca 2+ ] i , accompanied by depolarization, followed by a sustained [Ca 2+ ] i response. Progesterone-induced acrosome reaction is also blocked by DHPs, but the role of VOCCs in this process is disputed (Publicover and Barratt, 1999). Although sperm dysfunction is the single most common cause of human infertility (Hull et al., 1985; Irvine, 1998 The acrosome reaction is a key event in fertilization. Current models for induction of the acrosome reaction incorporate a necessary influx of Ca 2+ , which is mediated by agonistinduced gating of ion channels in the sperm plasma membrane. The difficulty of applying electrophysiological techniques to spermatozoa has severely hampered studies on the expression of functional ion channels in these cells. However, during the last few years, a combination of molecular and physiological techniques (applied to immature spermatogenic cells) has elucidated both the expression of Ca 2+ channels in male germ cells and their role in induction of the acrosome reaction. It now appears that a range of voltageoperated Ca 2+ channels, similar to those that occur in somatic cells, is expressed in spermatozoa. Male rodent germ cells express a low-voltage activated (...

Ion currents modulating oocyte maturation in animals

“…L-type calcium channels, however, do not represent the unique type of calcium channels found in ascidian oocytes that may play a role during oogenesis. Recently, in other ascidian species, we observed, for the first time in oocytes, T-type calcium channels [Gallo et al 2012], which are typically involved in sperm physiology [Jagannathan et al 2002]. This novel finding suggests new insights for the mechanism of calcium currents during oocyte maturation.…”

Acquired Cadmium Resistance in Metallothionein-I/II(–/–) Knockout Cells: Role of the T-Type Calcium Channel Cacnα1Gin Cadmium Uptake

“…T-type Ca 2ϩ channels are "activated" or opened by low-voltage currents close to the resting membrane potential of the cell. High extracellular concentrations of K ϩ are often used as a depolarizing stimulus to activate voltage-dependent Ca 2ϩ channels and therefore increase Ca 2ϩ influx into cells (Jagannathan et al, 2002). Thus, our observation that Cd 2ϩ uptake by MT(Ϫ/Ϫ) parental cells was unchanged by increased K ϩ concentrations is inconsistent with a voltage activation mechanism.…”

Ion currents involved in gamete physiology

“…In human spermatozoa, along with the role of Na + currents activated by progesterone stimulus (Patrat et al, 2000), the existence of voltage gated Ca 2+ currents was demonstrated (Linares-Hernandez et al, 1998), however their relation with the AR induction is still under investigation since the many indirect evidences reported (Darszon et al, 2011;Jagannathan et al, 2002). Among the mechanisms proposed for gating plasma membrane Ca 2+ currents a capacitating Ca 2+ entry mechanism play a relevant role.…”