Acid Extrusion from Human Spermatozoa Is Mediated by Flagellar Voltage-Gated Proton Channel

SummaryHuman 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.PaperFlick To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowHelp with MP4 filesOptionsDownload video (25618 K)

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► Whole-cell patch-clamp recordings of human spermatozoa reveal high proton conductance
► This conductance is due to proton channel Hv1 located in the sperm flagellum
► Voltage, an alkaline environment, and anandamide activate Hv1 while zinc inhibits it
► Hv1 activation induces intracellular alkalinization, known to activate sperm motility