Abstract
Small-conductance Cl− channels (0.3-0.4 pS) are abundantly present in the basolateral membrane of rabbit and rat parietal cells and have unique physiological roles. This Cl− channel has a housekeeping role through dominating the cell membrane potential, and the channel is activated via prostaglandin E2/ nitric oxide/ cyclic GMP-dependent pathway. The channel activity is inhibited by pertussis toxin-insensitive G-protein-mediated production of superoxide anion (O2−). Recently, we found that interleukin-1β (IL-1β) inhibited the channel activity. In the whole-cell patch-clamp recordings, the intracellular addition of superoxide dismutase, a scavenger of O2−, and GDPβS abolished the IL-1β-induced inhibition of the Cl− current. Northern blot analysis showed that Gα13 mRNA was highly expressed in rabbit gastric parietal cells. Gα12 mRNA was also expressed in the parietal cells. In the dihydrofluorescein diacetate-loaded single parietal cells in gastric glands, IL-1β stimulated the production of oxygen radicals. Y-27632, a specific Rho-kinase inhibitor, and fluvastatin, an indirect inhibitor for Rho proteins, significantly inhibited the IL-1β-induced effects on the channel activity and production of oxygen radicals. IL-1β activated Rho in the parietal cells. We suggest that IL-1β inhibits the small-conductance Cl− channels of rabbit gastric parietal cells by G12/G13-mediated Rho/Rho-kinase-dependent production of O2−. [Jpn J Physiol 55 Suppl:S44 (2005)]
