title: Pharmacological profile of inhibition of the chloride channels activated by extracellular acid in cultured rat Sertoli cells.
abstract: Sertoli cells from mammalian testis are key cells involved in the development and maintenance of stem cell spermatogonia as well as in the secretion of a Cl(-) and K(+)-rich fluid into the lumen of seminiferous tubules. The pharmacology and contribution of Cl(-) channels to the physiology of Sertoli cells were investigated using whole-cell patch clamp and iodide efflux experiments applied to cultured rat Sertoli cells. We characterized an outwardly rectifying Cl(-) current stimulated by various acid species including the physiologically relevant lactic acid. Using the iodide efflux technique, the pharmacological properties of this Cl(-) current, noted ICl(acid), revealed Ca(2+)-independent inhibition by DIDS (IC(50) = 27 microM), glibenclamide (IC(50) = 31 microM) and DPC (IC(50) = 86 microM). ICl(acid) was neither affected by calix[4]arene nor by 9-AC. The order of potency for inhibition of ICl(acid) is DIDS approximately glibenclamide > DPC >> calix[4]arene, 9-AC. For comparison, the inhibitory profile of the swelling- and ATP-activated Cl(-) currents in Sertoli cells is DPC = DIDS >> glibenclamide = 9-AC for ICl(swell) and DPC = 9-AC = DIDS >> glibenclamide for ICl(ATP). This description provides new insights into the physiology and pharmacology of the endogenous Cl(-) channels expressed and potentially involved in fluid secretion in Sertoli cells.
authors.affiliation: Institut de Physiologie et de Biologie Cellulaires CNRS UMR 6187, Université de Poitiers, 86022 Poitiers, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Auzanneau
authors.forename: Caroline
authors.initials: C
authors.lastname: Norez
authors.forename: Sabrina
authors.initials: S
authors.lastname: Noël
authors.forename: Chantal
authors.initials: C
authors.lastname: Jougla
authors.forename: Frédéric
authors.initials: F
authors.lastname: Becq
authors.forename: Clarisse
authors.initials: C
authors.lastname: Vandebrouck
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D048429:Cell Size / Q000187:drug effects*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D002712:Chlorides / Q000378:metabolism*; D004594:Electrophysiology; D005905:Glyburide / Q000378:metabolism / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007038:Hypotonic Solutions; D015640:Ion Channel Gating / Q000502:physiology*; D008297:Male; D018408:Patch-Clamp Techniques / Q000379:methods / Q000662:veterinary; D051381:Rats; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000378:metabolism / Q000502:physiology*
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D007038:Hypotonic Solutions; D000255:Adenosine Triphosphate; D005905:Glyburide