Sperm ion channels: molecular targets for the next generation of contraceptive medicines?

Investigation of ion channel biology continues to be an ever-expanding field of research. The ability of ion channels to regulate membrane potential and intracellular ionic milieu, such as Ca21, accords them a central role in varied cellular processes that govern excitability, action potential characteristics, stimulus-secretion coupling, cell volume regulation, and epithelial electrolyte transport. The importance of Ca21 ions in regulating diverse processes in sperm, including motility and acrosome reaction, has been well documented (Dan, 1954; Bredderman et al, 1971; Yanagimachi and Usui, 1974; Young and Nelson, 1974). However, the molecular nature of the ion channels or ion transport mechanisms involved has only recently begun to emerge despite the fact that several voltage-gated and ligand-gated channels have been cloned, expressed, and localized in sperm (Darszon et al, 1999). Attention to ion channels as drug targets for contraception has grown with the realization that certain channel subunits are localized exclusively in sperm, that selective knockdown of subunits can lead to infertility without untoward effects, and the rationale that selective inhibitors and/or openers of ion channels could interfere with sperm function. The state of current research includes more recently discovered ion channel subunits and derived combinations, elucidation of their physiological roles in relation to sperm biology and proof-of-principle studies using pharmacological and/or gene knockout approaches. Several publications have reviewed in detail the physiological basis of sperm function, including the role of ion channels (Darszon et al, 1999; Jagannathan et al, 2002). The scope of this review is to update recent advances in sperm ion channel biology in mammals, current directions