Dual effect of nitric oxide on ATP-sensitive K+ channels in rat pancreatic β cells
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We have previously shown that NO has stimulatory and inhibitory effects on insulin secretion at low and high concentrations, respectively. The present study investigated effects of NO on KATP channels of rat β cells by patch clamp analysis to elucidate the mechanism for the dual effect. NOC7 at 0.5 μM suppressed KATP channels activated by diazoxide in the cell-attached and perforated whole-cell modes but failed to suppress them in the inside-out mode. The inhibitory effect in the cell-attached mode was abolished by the soluble guanylate cyclase inhibitor ODQ and by the protein kinase G inhibitor KT5823. Moreover, 0.5 μM NOC7 failed to suppress the channel activity in the presence of the mitochondrial uncoupler FCCP. In contrast, 10 μM NOC7 activated KATP channels in the cell-attached and perforated whole-cell modes, although it had no effect on the channels in the inside-out mode. The KATP currents evoked by 10 μM NOC7 in the cell-attached mode were not inhibited by ODQ. The dual effect of NOC7 at 0.5 and 10 μM was observed in the same patch. Taken together, these results suggest that low-concentration NO exerts an inhibitory effect on KATP channels of β cells, which is induced through the cGMP/protein kinase G pathway, whereas high-concentration NO activates KATP channels through the mechanism independent of cGMP.
KeywordsPatch clamp Pancreatic β cell K+ currents NO cGMP Single channel ATP
This study was supported by a Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science and by Suzuken Memorial Foundation.
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