Effects of Nicorandil on the cAMP-dependent Cl- current in Guinea-Pig ventricular cells

In guinea-pig cardiomyocytes,a camp-dependent cl- current (icl,camp) flows through a cardiac isoform of the cystic fibrosis transmembrane conductance regulator (cftr),which be-longs to a family of the atp-binding cassette (abc) proteins. although several k+-channel open-ers and sulfonylurea atp-sensitive k+ (katp)-channel blockers reportedly inhibit icl,camp,effects of nicorandil on the cl- current have not been evaluated. this study was conducted to examine the effects of nicorandil on icl,camp in isolated guinea-pig ventricular cells using patch clamp tech-niques. nicorandil in concentrations higher than 300 μm enhanced the icl,camp preactivated by 0.1 μm isoproterenol. the isoproterenol-induced icl,camp was inhibited by 100 μm glibenclamide,but not by 100 μm pinacidil. snap (s-nitroso-n-acetyl-d,l-penicillamine,10 μm),a nitric oxide (no) donor,similarly enhanced the isoproterenol-induced icl,camp. however,sg-86,a denitrated metabo-lite possessing k+ channel-opening action,failed to enhance the cl- current. when the icl,camp was activated by 3-isobutyl-1-methylxanthine (ibmx,30 μm),either nicorandil or snap failed to enhance the isoproterenol-induced icl,camp. thus,nicorandil enhances icl,camp in guinea-pig cardio-myocytes through an increase in intracellular cgmp,although direct modulation of icl,camp by no cannot be completely excluded. ©2010 the japanese pharmacological society.