Abstract: | We previously demonstrated that nitric oxide (NO) stimulates thebasolateral small-conductance K+channel (SK) via a cGMP-dependent pathway M. Lu and W. H. Wang. Am. J. Physiol. 270 (Cell Physiol. 39): C1336-C1342,1996]. Because NO at high concentration has been shown to reactwith superoxide (O2) to formperoxynitrite (OONO)W. A. Pryor and G. L. Squadrito. Am. J. Physiol. 268 (Lung Cell. Mol.Physiol. 12): L699-L722, 1995 and M. S. Wolin.Microcirculation 3: 1-17,1996], we extended our study to examine, using patch-clamp technique, the effect of high concentrations of NO on SK in cortical collecting duct (CCD) of rat kidney. Addition of NO donors100-200 µMS-nitroso-N-acetyl-penicillamine(SNAP) or sodium nitroprusside (SNP)] reduced channel activity,defined as the product of channel number and open probability, to 15 and 25% of the control value, respectively. The inhibitory effect ofNO was completely abolished in the presence of 10 mM Tiron, anintracellular scavenger of O2. NOdonors, 10 µM SNAP or SNP, which stimulate channel activity undercontrol conditions, can also inhibit SK in the presence of anO2 donor, pyrogallol, or in thepresence of an inhibitor of superoxide dismutase, diethyldithiocarbamic acid. The inhibitory effect of NO is still observed in the presence ofexogenous cGMP, suggesting that the NO-induced inhibition is not theresult of decreased cGMP production. We conclude that the inhibitoryeffect of NO on channel activity results from an interaction between NOand O2. |