Amino Acid Neurotransmitter Receptor/Chloride Channels of Mammalian Sperm and the Acrosome Reaction1

Abstract

Two different amino acid neurotransmitter receptor/Cl-channels, a gamma-aminobutyric acid (GABA) receptor-like/Cl- channel and a glycine receptor/Cl- channel, have recently been found in mammalian sperm and shown to be involved in the sperm acrosome reaction (AR), an exocytotic event essential to mammalian fertilization. The identity of the receptor/channel involved in the AR depends upon the stimulatory ligand. The AR initiated by the egg zona pellucida requires the participation of the sperm glycine receptor/Cl- channel, whereas the AR initiated by another putative physiological AR initiator, progesterone, involves the sperm GABA receptor-like/Cl- channel. Cl- efflux through the latter has been shown to occur during the progesterone-initiated AR. Activation of sperm amino acid neurotransmitter receptor/Cl- channels may result in plasma membrane depolarization and thereby exert at least a partial control over voltage-sensitive sperm Ca2+ channels and Ca2+ influx important to the AR.

GABA exists as a negative regulator of cell proliferation in spermaogonial stem cells

“…GABA is a versatile molecule with diverse functions in organisms from bacteria through plants to higher mammals [30]. In the male reproductive system, GABA has been shown to promote the acrosome reaction of spermatozoa [31,32]. However, the precise physiological function of GABA in germ cell development remains unclear.…”

Evidence that anandamide‐signaling regulates human sperm functions required for fertilization

“…Sperm acquire the capacity to fertilize eggs following removal from seminal plasma and exposure for several hours to female reproductive tract fluids in vivo, or by incubation in appropriate culture medium in vitro (Meizel, 1985;Burkman, 1990Burkman, , 1995Yanagimachi, 1994;Meizel, 1997;Kopf et al, 1999). ''Capacitated'' sperm exhibit vigorous hyperactivated motility required for fertilization, and can undergo physiological acrosome reactions at the egg's surface (Wassarman, 1987;Burkman, 1990Burkman, , 1995Yanagimachi, 1994;Kang-Decker et al, 2001).…”

Biphasic Effect of GABA on Rat Sperm Acrosome Reaction: Involvement of GABA A and GABA B Receptors

“…Progesterone induces AR in human sperm by interacting with a steroid receptor located in the plasma membrane. This membrane receptor is distinctly di erent from the classical nuclear receptor [4,22,26,30] and may be related to the GABA A receptor=Cl 7 channel [21].…”