SLO3 K+ Channels Control Calcium Entry through CATSPER Channels in Sperm [Developmental Biology]

September 30th, 2014 by Chavez, J. C., Ferreira Gregorio, J., Butler, A., Treviňo, C. L., Darszon, A., Salkoff, L., Santi, C. M.

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 while 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 manuscript 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 inintracellular 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 sperm specific Na*/H* exchanger (sNHE) possess a putative voltage sensor that might be activated by membrane hyperpolarization, thus increasing the voltage sensitivity of internal alkalization.