Free Access
Reprod. Nutr. Dev.
Volume 46, Number 3, May-June 2006
Page(s) 241 - 255
Published online 30 May 2006
Reprod. Nutr. Dev. 46 (2006) 241-255
DOI: 10.1051/rnd:2006013

Pharmacological profile of inhibition of the chloride channels activated by extracellular acid in cultured rat Sertoli cells

Céline Auzanneau, Caroline Norez, Sabrina Noël, Chantal Jougla, Frédéric Becq and Clarisse Vandebrouck

Institut de Physiologie et de Biologie Cellulaires CNRS UMR 6187,Université de Poitiers, 86022 Poitiers, France

(Received 4 November 2005; accepted 24 February 2006; published online 13 June 2006)

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 $_{\rm acid}$, revealed Ca2+-independent inhibition by DIDS (IC50 = 27 micronM), glibenclamide (IC50 = 31 micronM) and DPC (IC50 = 86 micronM). ICl $_{\rm acid}$ was neither affected by calix[4]arene nor by 9-AC. The order of potency for inhibition of ICl $_{\rm acid}$ is DIDS $\approx $ 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 $_{\rm swell}$ and DPC = 9-AC = DIDS $>\!>$ glibenclamide for ICl $_{\rm ATP}$. 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.

Key words: Cl- channels / pharmacology / proton-activation / ATP / cell volume / glibenclamide

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© INRA, EDP Sciences 2006