NONSPECIFIC INHIBITION OF ADENOSINE-ACTIVATED K-PIG ATRIAL MYOCYTES( CURRENT BY GLIBENCLAMIDE IN GUINEA)

The ATP-sensitive K+ (K-ATP) channel blocker glibenclamide was reporte d to inhibit the K+ current activated by adenosine. This study investi gated whether the inhibition by glibenclamide of the adenosine-induced current is due to a specific blockade of K-ATP channels in guinea pig atrial myocytes. In the absence of adenosine, the basal background cu rrent was an inward rectifier K+ current (I-K1). Glibenclamide at conc entrations of 10, 30, and 100 mu M reduced the basal background K+ cur rent by 15 +/- 6, 43 +/- 10, and 63 +/- 11%, respectively. In the pres ence of adenosine (10 mu M), glibenclamide (30 mu M) decreased the ade nosine-induced K+ current by 39 +/- 3%. A similar inhibitory effect of glibenclamide on the outward K+ currents activated by either the musc arinic agonist carbachol or the nonhydrolyzable GTP analogue guanosine 5'-[gamma-thio]triphosphate was observed. A low concentration (1 mu M ) of glibenclamide did not significantly attenuate the current elicite d by adenosine, although it completely abolished the outward K+ curren t activated by pinacidil, a K-ATP channel opener. Thus we conclude tha t the inhibition of adenosine-induced K+ current by glibenclamide at h igh concentrations (>1 mu M) is not due to a specific blockade at K-AT P channels, but rather, resulted from a blockade of I-K1.