title: SLO3 K+ channels control calcium entry through CATSPER channels in sperm.
abstract: 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.
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110 and; Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), 62210 Cuernavaca, México.
authors.forename: Julio César
authors.initials: JC
authors.lastname: Chávez
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110 and.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Ferreira
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110 and.
authors.forename: Alice
authors.initials: A
authors.lastname: Butler
authors.affiliation: Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), 62210 Cuernavaca, México.
authors.forename: José Luis
authors.initials: JL
authors.lastname: De La Vega Beltrán
authors.affiliation: Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), 62210 Cuernavaca, México.
authors.forename: Claudia L
authors.initials: CL
authors.lastname: Treviño
authors.affiliation: Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), 62210 Cuernavaca, México.
authors.forename: Alberto
authors.initials: A
authors.lastname: Darszon
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110 and.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Salkoff
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110 and.
authors.forename: Celia M
authors.initials: CM
authors.lastname: Santi
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000737:chemistry; D001692:Biological Transport; D002118:Calcium / Q000737:chemistry; D015220:Calcium Channels / Q000378:metabolism*; D005298:Fertility; D005786:Gene Expression Regulation; D006863:Hydrogen-Ion Concentration; D015759:Ionomycin / Q000737:chemistry; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011522:Protons; D012964:Sodium / Q000737:chemistry; D013094:Spermatozoa / Q000378:metabolism*; D014634:Valinomycin / Q000737:chemistry
chemical_list: D001639:Bicarbonates; D015220:Calcium Channels; C488642:Catsper1 protein, mouse; C110627:Kcnu1 protein, mouse; D051036:Large-Conductance Calcium-Activated Potassium Channels; D011522:Protons; D014634:Valinomycin; D015759:Ionomycin; D012964:Sodium; D002118:Calcium
keywords: Calcium; Calcium Channel; Potassium Channel; Sperm; Spermatozoa; pH Regulation