Simultaneous knockout of slo3 and catsper1 abolishes all alkalization- and voltage-activated current in mouse spermatozoa

Xu Hui Zeng, Betsy Navarro, Xiao Ming Xia, David E. Clapham, Christopher J. Lingle

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

During passage through the female reproductive tract, mammalian sperm undergo a maturation process termed capacitation that renders sperm competent to produce fertilization. Capacitation involves a sequence of changes in biochemical and electrical properties, the onset of a hyperactivated swimming behavior, and development of theability to undergo successful fusion and penetration with an egg. In mouse sperm, the development of hyperactivated motility is dependent on cytosolic alkalization that then results in an increase in cytosolic Ca2+.The elevation of Ca2+ is thought to be primarily driven by the concerted interplay of two alkalization-activated currents, a K+ current (KSPER) composed of pore-forming subunits encoded by the Kcnu1gene (also termed Slo3) and a Ca2+ current arising from a family of CATSPER subunits. After deletion of any of four CATSPER subunit genes (CATSPER1-4), the major remaining current in mouse sperm is alkalization-activated KSPER current. After genetic deletion of the Slo3 gene, KSPER current is abolished, but there remains a small voltage-activated K+current hypothesized to reflect monovalent flux through CATSPER. Here, we address two questions. First, does the residual outward K+current present in the Slo3-/-sperm arise from CATSPER? Second, can any additional membrane K+currents be detected in mouse sperm by patch-clamp methods other than CATSPER and KSPER? Here, using mice bred to lack both SLO3 and CATSPER1 subunits,we show conclusively that the voltage-activated outward current present in Slo3-/- sperm is abolished when CATSPER is also deleted. Any leak currents that may play a role in setting the resting membrane potentialinnoncapacitated sperm are likely smaller than the pipette leak current and thus cannot be resolved within the limitation of the patch-clamp technique. Together, KSPER and CATSPER appear to be the sole ion channels present in mouse sperm that regulate membrane potential and Ca2+ influx in response to alkalization.

Original languageEnglish
Pages (from-to)305-313
Number of pages9
JournalJournal of General Physiology
Volume142
Issue number3
DOIs
StatePublished - 2013

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