Transient receptor potential vanilloid 1 (TRPV1) channels in cultured rat Sertoli cells regulate an acid sensing chloride channel.

Sertoli cells provide a controlled microenvironment for regulation and maintenance of spermatogenesis for which an acidic milieu is crucial for male fertility. Sertoli cells also contribute to protection of spermatogenetic cells. Here, we showed that TRPV1 is expressed in rat Sertoli cells and regulates an acid sensing Cl(-) channel (ASCC). The expression of TRPV1 in rat Sertoli cells was demonstrated by RT-PCR, immunostaining and calcium measurement experiments. ASCC activity was inhibited by capsaicin (IC(50)=214.3+/-1.6 nM), olvanil (IC(50)=400+/-1.7 pM) and resiniferatoxin (IC(50)=9.3+/-1.5 nM) but potentiated by capsazepine (EC(50)=5.3+/-1.3 microM) and ruthenium red (EC(50)=2.3+/-1.5 microM). In the human airway epithelial cell line Calu-3 in which ASCC can be detected but not TRPV1, capsaicin and capsazepine were without any effect. Finally the application of the non-steroidal anti-inflammatory drug ibuprofen prevented the control of ASCC by TRPV1. Our study provides the first evidence for a regulation by TRPV1 of an acid sensing chloride channel in rat Sertoli cells. TRPV1 and ASCC may thus be considered as new potential physiological regulators of spermatogenesis and targets for pharmacological treatments of reproductive disorders as cryptorchidism, Sertoli cell tumors or torsion of the spermatic cord.

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

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.