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

Here we show how a sperm-specific potassium channel (SLO3) controls Ca(2+) entry into sperm through a sperm-specific Ca(2+) 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 Ca(2+) entry. These two channels may be functionally connected, but it had not been demonstrated that SLO3-dependent hyperpolarization is required for Ca(2+) entry through CATSPER channels, nor has a functional mechanism linking the two channels been shown. In this study we show that Ca(2+) 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 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.

Chávez JC ，Ferreira JJ ，Butler A ，De La Vega Beltrán JL ，Treviño CL ，Darszon A ，Salkoff L ，Santi CM ... -  《-》

SLO3 auxiliary subunit LRRC52 controls gating of sperm KSPER currents and is critical for normal fertility.

Zeng XH ，Yang C ，Xia XM ，Liu M ，Lingle CJ ... -  《-》

Deletion of the Slo3 gene abolishes alkalization-activated K+ current in mouse spermatozoa.

Zeng XH ，Yang C ，Kim ST ，Lingle CJ ，Xia XM ... -  《-》

Simultaneous knockout of Slo3 and CatSper1 abolishes all alkalization- and voltage-activated current in mouse spermatozoa.

Zeng XH ，Navarro B ，Xia XM ，Clapham DE ，Lingle CJ ... -  《-》

Ion permeabilities in mouse sperm reveal an external trigger for SLO3-dependent hyperpolarization.

Chávez JC ，de la Vega-Beltrán JL ，Escoffier J ，Visconti PE ，Treviño CL ，Darszon A ，Salkoff L ，Santi CM ... -  《PLoS One》