Nonspecific inhibition of adenosine-activated K+ current by glibenclamide in guinea pig atrial myocytes.
The ATP-sensitive K+ (KATP) channel blocker glibenclamide was reported to inhibit the K+ current activated by adenosine. This study investigated whether the inhibition by glibenclamide of the adenosine-induced current is due to a specific blockade of KATP channels in guinea pig atrial myocytes. In the absence of adenosine, the basal background current was an inward rectifier K+ current (IK1). Glibenclamide at concentrations of 10, 30, and 100 microM reduced the basal background K+ current by 15 +/- 6, 43 +/- 10, and 63 +/- 11%, respectively. In the presence of adenosine (10 microM), glibenclamide (30 microM) decreased the adenosine-induced K+ current by 39 +/- 3%. A similar inhibitory effect of glibenclamide on the outward K+ currents activated by either the muscarinic agonist carbachol or the nonhydrolyzable GTP analogue guanosine 5'-[gamma-thio]triphosphate was observed. A low concentration (1 microM) of glibenclamide did not significantly attenuate the current elicited by adenosine, although it completely abolished the outward K+ current activated by pinacidil, a KATP channel opener. Thus we conclude that the inhibition of adenosine-induced K+ current by glibenclamide at high concentrations (> 1 microM) is not due to a specific blockade of KATP channels, but rather, resulted from a blockade of IK1.
Song
Y
Y
Department of Medicine, University of Florida, Gainesville 32610, USA.
Srinivas
M
M
Belardinelli
L
L
D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D016275:Atrial Function / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D004553:Electric Conductivity; D005905:Glyburide / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006168:Guinea Pigs; D009206:Myocardium / Q000166:cytology; D020110:Pinacidil; D011188:Potassium / Q000037:antagonists & inhibitors* / Q000502:physiology*; D011930:Reaction Time / Q000187:drug effects
D006146:Guanidines; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D020110:Pinacidil; D002217:Carbachol; D000241:Adenosine; D011188:Potassium; D005905:Glyburide