Volume-activated chloride channels in mice Leydig cells

Autor(es)

Poletto Chaves, Luiz Artur ^[1] ; Varanda, Wamberto Antonio ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Dept Physiol, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY; v. 457, n. 2, p. 493-504, NOV 2008.
• Citações Web of Science: 11

Resumo

Production and secretion of testosterone in Leydig cells are mainly controlled by the luteinizing hormone (LH). Biochemical evidences suggest that the activity of Cl(-) ions can modulate the steroidogenic process, but the specific ion channels involved are not known. Here, we extend the characterization of Cl(-) channels in mice Leydig cells (50-60 days old) by describing volume- activated Cl(-) currents (I(Cl,swell)). The amplitude of I(Cl,swell) is dependent on the osmotic gradient across the cell membrane, with an apparent EC(50) of similar to 75 mOsm. These currents display the typical biophysical signature of volume- activated anion channels (VRAC): dependence on intracellular ATP, outward rectification, inactivation at positive potentials, and selectivity sequence (I(-)>Cl(-)>F(-)). Staurosporine (200 nM) did not block the activation of I(Cl), swell. The block induced by 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB; 128 mu M), SITS (200 mu M), ATP (500 mu M), pyridoxalphosphate-6- azophenyl-2',4'-disulfonate (PPADS; 100 mu M), and Suramin (10 mu M) were described by the permeant blocker model with apparent dissociation constant at 0 mV K(d)(0) and fractional distance of the binding site (delta) of 334 mu M and 47%, 880 mu M and 35%, 2,100 mu M and 49%, 188 mu M and 27%, and 66.5 mu M and 49%, respectively. These numbers were derived from the peak value of the currents. We conclude that ICl, swell in Leydig cells are activated independently of purinergic stimulation, that Suramin and PPADS block these currents by a direct interaction with VRAC and that ATP is able to permeate this channel. (AU)

• Processo FAPESP: 06/50954-7 - Correntes iônicas e receptores na fisiologia de células excitáveis e não excitáveis
• Beneficiário: Wamberto Antonio Varanda
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 03/10492-6 - Interacao entre canais para cloreto e receptores purinergicos em celulas de leydig de camundongos.
• Beneficiário: Luiz Artur Poletto Chaves
• Modalidade de apoio: Bolsas no Brasil - Doutorado