Acid extrusion from human spermatozoa is mediated by flagellar voltage-gated proton channel.
Human spermatozoa are quiescent in the male reproductive system and must undergo activation once introduced into the female reproductive tract. This process is known to require alkalinization of sperm cytoplasm, but the mechanism responsible for transmembrane proton extrusion has remained unknown because of the inability to measure membrane conductance in human sperm. Here, by successfully patch clamping human spermatozoa, we show that proton channel Hv1 is their dominant proton conductance. Hv1 is confined to the principal piece of the sperm flagellum, where it is expressed at unusually high density. Robust flagellar Hv1-dependent proton conductance is activated by membrane depolarization, an alkaline extracellular environment, endocannabinoid anandamide, and removal of extracellular zinc, a potent Hv1 blocker. Hv1 allows only outward transport of protons and is therefore dedicated to inducing intracellular alkalinization and activating spermatozoa. The importance of Hv1 for sperm activation makes it an attractive target for controlling male fertility.
Department of Physiology, University of California, San Francisco, UCSF Mail Code 2140, Genentech Hall, Room N272F, 600 16(th) Street, San Francisco, CA 94158, USA.
Polina V
PV
Lishko
Inna L
IL
Botchkina
Andriy
A
Fedorenko
Yuriy
Y
Kirichok
D020101:Acrosome Reaction; D000818:Animals; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D051379:Mice; D013075:Sperm Capacitation; D013081:Sperm Motility; D013082:Sperm Tail / Q000378:metabolism; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism
C510235:HVCN1 protein, human; D007473:Ion Channels