title: Pharmacology of hSlo3 channels and their contribution in the capacitation-associated hyperpolarization of human sperm.
abstract: Slo3 channels (mSlo3) primarily mediate mouse sperm K(+) currents and are essential for the capacitation-associated hyperpolarization (CAH). Whether Slo3 and/or Slo1, two Slo family K(+) channels are functionally expressed in human sperm is controversial. Our recent pharmacological studies of the human sperm CAH suggested the participation of both. Lack of a detailed pharmacology of heterologously expressed human Slo3 (hSlo3) prevented precisely identifying the K(+) channel(s) involved. In the present report, we compare the pharmacological profile of expressed hSlo3 in CHO cells with that of the CAH to advance this matter. Whole-cell patch-clamp recordings showed that hSlo3 currents are inhibited: significantly by progesterone, Ba(2+) and quinidine; partially by Penitrem A and Charybdotoxin; and poorly by Iberiotoxin and Slotoxin. Surprisingly, hSlo3 currents were resistant to Clofilium and 60 mM TEA(+) which inhibit mSlo3. Pharmacological comparison of the CAH and hSlo3 profiles indicates in addition to hSlo3, other K(+) channels, possibly Slo1, may participate in CAH. The pharmacological profile of heterologously expressed hSlo3 channels differs from that of mSlo3 K(+) channels, consistent with species-specific differences observed among other sperm ion channels. While the pharmacological correlation analysis of the hSlo3 currents and the CAH confirmed the participation of hSlo3 channels, it suggests that additional K(+) channels may be involved, in particular Slo1 channels.
authors.affiliation: Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, Mexico.
authors.forename: Oscar
authors.initials: O
authors.lastname: Sánchez-Carranza
authors.affiliation: Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, Mexico.
authors.forename: Paulina
authors.initials: P
authors.lastname: Torres-Rodríguez
authors.affiliation: Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, Mexico.
authors.forename: Alberto
authors.initials: A
authors.lastname: Darszon
authors.affiliation: Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, Mexico. Electronic address: ctrevino@ibt.unam.mx.
authors.forename: Claudia L
authors.initials: CL
authors.lastname: Treviño
authors.affiliation: Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, Mexico. Electronic address: iglogo@ibt.unam.mx.
authors.forename: Ignacio
authors.initials: I
authors.lastname: López-González
mesh_terms: D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D006801:Humans; D066298:In Vitro Techniques; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D013075:Sperm Capacitation / Q000502:physiology*; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism*
chemical_list: C577767:KCNU1 protein, human; C110627:Kcnu1 protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins
keywords: CHO cells; Capacitation-induced hyperpolarization; Flow cytometry; Human Slo3 K(+) channels; αKTX subfamily toxins