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pH-Dependent Regulation of Calcium Influx

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Science's STKE  14 Feb 2006:
Vol. 2006, Issue 322, pp. tw59
DOI: 10.1126/stke.3222006tw59

Sperm cells become hyperactivated at the site of fertilization, vigorously beating their flagellae in a process that enables them to penetrate the cumulus and the zona pellucida and thereby fertilize the ovum. Although hyperactivation is thought to involve calcium influx through plasma membrane ion channels, the details have been unclear. Kirichok et al. were able to obtain a tight seal and perform whole-cell and perforated-patch recordings of ion currents in spermatozoa by establishing the patch on the cytoplasmic droplet, a remnant of precursor germ cell cytoplasm found on the midpiece of the sperm cell flagellum. They identified an inward current in the sperm of wild-type mice but not of those lacking CatSper1, a putative ion channel required for hyperactivation. By recording from sperm fragments containing either the midpiece and head or the midpiece and the principal piece of the flagellum, the authors were able to determine that the current was localized to the principal piece (where CatSper1 is located). Their analysis indicated that, under physiological conditions, this current (which they called ICatsPer) should be active and highly calcium-selective. ICatsPer was markedly potentiated by intracellular alkalinization; thus, the authors propose that the increase in intraflagellar calcium concentration required for hyperactivation depends on the pH-dependent activation of calcium influx through the sperm-specific CatSper calcium channel.

Y. Kirichok, B. Navarro, D. E. Clapham, Whole-cell patch-clamp measurements of spermatozoa reveal an alkaline-activated Ca2+ channel. Nature 439, 737-740 (2006). [PubMed]