The SLO3 sperm‐specific potassium channel plays a vital role in male fertility

Abstract

a b s t r a c tHere we show a unique example of male infertility conferred by a gene knockout of the spermspecific, pH-dependent SLO3 potassium channel. In striking contrast to wild-type sperm which undergo membrane hyperpolarization during capacitation, we found that SLO3 mutant sperm undergo membrane depolarization. Several defects in SLO3 mutant sperm are evident under capacitating conditions, including impaired motility, a bent ''hairpin" shape, and failure to undergo the acrosome reaction (AR). The failure of AR is rescued by valinomycin which hyperpolarizes mutant sperm. Thus SLO3 is the principal potassium channel responsible for capacitation-induced hyperpolarization, and membrane hyperpolarization is crucial to the AR.Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

Flagellar ion channels of sperm: similarities and differences between species

“…Slo3 was also sensitive to Ba 2+ , quinine and mibefradil that all reversibly inhibited murine Slo3 [29]. The identity and importance of the Slo3 channel for murine sperm physiology was confirmed by recordings from Slo3-deficient mice that also display severely reduced male fertility [25,31]. While Slo3 was also expected to form the potassium channel of human sperm, recent recording from ejaculated human spermatozoa indicates that in clear contrast to murine sperm, human sperm potassium current (KSper) is pH-independent and sensitive to [Ca 2+ ] i [20].…”

“…Noncapacitated epididymal murine spermatozoa are slightly depolarized at about −40 mV, however they hyperpolarize up to −60 mV upon capacitation [137]. This effect is attributed to potassium permeability and two members of the Slo family of potassium channels have been recently proposed to play a role in this process [21,25,26,29,31,33,[138][139][140][141]. Slo3 (Kcnu1), a pH-sensitive, calcium-independent and weakly voltage-sensitive channel, has been identified as the principal potassium channel in murine sperm [25,26,29,31,33,[141][142][143].…”

Cl− Channels and Transporters in Sperm Physiology

“…Motility is one of the most important functions carried out by the sperm because it is essential to achieve fertilization. Indeed, several sperm motility defects can cause male sterility (e.g., sAC, PKA, sNHE, GAPDHs, CatSper, PMCA4, SLO3) (Esposito et al 2004 ;Miki et al 2004 ;Nolan et al 2004 ;Okunade et al 2004 ;Quill et al 2001 ;Ren et al 2001 ;Santi et al 2010 ;Wang et al 2007 ;Zeng et al 2011 ). Sperm motility is driven by the fl agellum, an appendage with an ultrastructure very similar to that of cilia.…”

“…Achieving whole-cell patch-clamp recordings became more feasible when Kirichok et al ( 2006 ) were able to seal the cytoplasmic droplet of mouse epididymal spermatozoa and then mature human spermatozoa (Kirichok and Lishko 2011 ). This novel strategy is allowing the characterization of spermspecifi c channels such as CatSper (Kirichok et al 2006 ) and SLO3 (Navarro et al 2007 ;Santi et al 2010 ;Schreiber et al 1998 ;Zeng et al 2011 ), and of sperm anion channels that are present in other cell types Ferrera et al 2010 ). Additionally, a voltage-sensitive H + channel involved in the intracellular pH (pH i ) regulation in human sperm and less importantly in mouse sperm (Kirichok and Lishko 2011 ), and ATP-gated channels of the purinergic family, P2X2, in mouse epididymal sperm have been recorded (Navarro et al 2011 ).…”

“…When possible, eliminating the specifi c ion channel from spermatozoa might unravel its function (Kirichok et al 2006 ;Santi et al 2010 ). Initial glimpses of the properties of some sperm ion channels were derived from planar bilayers with incorporated sperm plasma membranes (reviewed by Darszon et al 1999 ).…”