Whole-cell patch-clamp measurements of spermatozoa reveal an alkaline-activated Ca2+ channel.
In mammals, sperm cells become motile during ejaculation and swim up the female reproductive tract. Before fertilization and to overcome various barriers, their motility must be hyperactivated, a motion that is characterized by vigorous asymmetric tail beating. Hyperactivation requires an increase in calcium in the flagella, a process that probably involves plasmalemmal ion channels. Numerous attempts in the past two decades to understand sperm cell channels have been frustrated by the difficulty of measuring spermatozoan transmembrane ion currents. Here, by using a simple approach to patch-clamp spermatozoa and to characterize whole-spermatozoan currents, we describe a constitutively active flagellar calcium channel that is strongly potentiated by intracellular alkalinization. This current is not present in spermatozoa lacking the sperm-specific putative ion channel protein, CatSper1. This plasma membrane protein of the six transmembrane-spanning ion channel superfamily is specifically localized to the principal piece of the sperm tail and is required for sperm cell hyperactivation and male fertility. Our results identify CatSper1 as a component of the key flagellar calcium channel, and suggest that intracellular alkalinization potentiates CatSper current to increase intraflagellar calcium and induce sperm hyperactivation.
Howard Hughes Medical Institute, Department of Cardiology, Children's Hospital and Harvard Medical School Enders 1309, Boston, Massachusetts 02115, USA.
Yuriy
Y
Kirichok
Betsy
B
Navarro
David E
DE
Clapham
D000468:Alkalies / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004553:Electric Conductivity; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects*; D017136:Ion Transport; D008297:Male; D051379:Mice; D009928:Organ Specificity; D018408:Patch-Clamp Techniques; D013082:Sperm Tail / Q000187:drug effects / Q000378:metabolism; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D013379:Substrate Specificity
D000468:Alkalies; D015220:Calcium Channels; C488642:Catsper1 protein, mouse; D002118:Calcium