TY - JOUR
T1 - SLO3 K+ channels control calcium entry through CATSPER channels in sperm
AU - Chávez, Julio César
AU - Ferreira, Juan José
AU - Butler, Alice
AU - De La Vega Beltrán, José Luis
AU - Treviño, Claudia L.
AU - Darszon, Alberto
AU - Salkoff, Lawrence
AU - Santi, Celia M.
N1 - Publisher Copyright:
© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2014/11/14
Y1 - 2014/11/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84911127364&partnerID=8YFLogxK
U2 - 10.1074/jbc.M114.607556
DO - 10.1074/jbc.M114.607556
M3 - Article
C2 - 25271166
AN - SCOPUS:84911127364
VL - 289
SP - 32266
EP - 32275
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 46
ER -