SLO3 K+ channels control calcium entry through CATSPER channels in sperm

Julio César Chávez, Juan José Ferreira, Alice Butler, José Luis De La Vega Beltrán, Claudia L. Treviño, Alberto Darszon, Lawrence Salkoff, Celia M. Santi

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Here we show how a sperm-specific potassium channel (SLO3) controls Ca2+ entry into sperm through a sperm-specific Ca2+ channel, CATSPER, in a totally unanticipated manner. The genetic deletion of either of those channels confers male infertility in mice. During sperm capacitation SLO3 hyperpolarizes the sperm, whereas CATSPER allows Ca2+ entry. These two channels may be functionally connected, but it had not been demonstrated that SLO3-dependent hyperpolarization is required for Ca2+ entry through CATSPER channels, nor has a functional mechanism linking the two channels been shown. In this study we show that Ca2+ entry through CATSPER channels is deficient in Slo3 mutant sperm lacking hyperpolarization; we also present evidence supporting the hypothesis that SLO3 channels activate CATSPER channels indirectly by promoting a rise in intracellular pH through a voltage-dependent mechanism. This mechanism may work through a Na+/H+ exchanger (sNHE) and/or a bicarbonate transporter, which utilizes the inward driving force of the Na+ gradient, rendering it intrinsically voltage-dependent. In addition, the spermspecific Na+/H+ exchanger (sNHE) possess a putative voltage sensor that might be activated by membrane hyperpolarization, thus increasing the voltage sensitivity of internal alkalization.

Original languageEnglish
Pages (from-to)32266-32275
Number of pages10
JournalJournal of Biological Chemistry
Volume289
Issue number46
DOIs
StatePublished - Nov 14 2014

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    Chávez, J. C., Ferreira, J. J., Butler, A., De La Vega Beltrán, J. L., Treviño, C. L., Darszon, A., Salkoff, L., & Santi, C. M. (2014). SLO3 K+ channels control calcium entry through CATSPER channels in sperm. Journal of Biological Chemistry, 289(46), 32266-32275. https://doi.org/10.1074/jbc.M114.607556