Ion channels in sperm physiology and male fertility and infertility

Abstract

Ion channels regulate the membrane potential and intracellular ionic concentration and thus serve a central role in various cellular processes. Several ion channels have been identified in the germ cells, including sperm, emphasizing their importance in male fertility and reproduction. The molecular mechanism of ion transport and the nature of the ion channels involved have begun to emerge only recently despite the fact that several ligand-gated and voltage-gated channels have been identified and localized on sperm. The presence of the sperm-associated cation channel (CatSper1-4) gene family, proton voltage-gated ion channel (Hv1), potassium voltage-gated ion channel (SLO3/KCNU1), sodium voltage-gated channel (NaV1.1-1.9), and the members of the transient receptor potential (TRP) channel family suggest an indispensable role for ion channels in sperm physiology and fertility potential. Ion channels are the key players in very important processes such as capacitation and the acrosome reaction, which are critical steps in sperm physiology preparing for fertilization. For example, CatSper, Hv1, SLO3, and TRP channel family members have been proposed to participate in the acrosome reaction, thereby making them most important for sperm fertility. Similarly, NaV channels could play a crucial role in noncapacitated sperm and in the initial capacitation steps. The role of ion channels seems indispensable for sperm fertility as evidenced by studies on animal models; however, the functional defects in infertile human males await further exploration. This article represents an update on the role of ion channels in sperm physiology, male fertility, and infertility.