Mechanism of the negative inotropic effect of adenosine in guinea pig atrial myocytes.
The ionic basis of the negative inotropic effect of adenosine on guinea pig atrial myocytes was studied. Membrane potentials and currents were measured using a whole cell patch-clamp technique. The contractility was assessed by video quantitation of cell twitch amplitude. Adenosine shortened action potential duration [measured at 90% repolarization (APD90)] and decreased twitch amplitude in a concentration-dependent manner. The maximal effects of adenosine (100 microM) were to reduce APD90 from 102 +/- 14 to 34 +/- 8 ms (n = 11) and twitch amplitude from 4.3 +/- 0.9 to 1.5 +/- 0.4 microns (n = 8). The concentration of adenosine that caused one-half of the maximal reductions of twitch amplitude and of APD90 was 0.6 microM. Reductions in APD90 and in twitch amplitude were parallel and highly correlated (r = 0.98). Decreases in twitch amplitude by adenosine could be mimicked by application of voltage-clamp pulses with durations similar to the durations of action potentials in the presence of adenosine. Clamp pulse could reverse adenosine-induced but not cadmium chloride-induced decreases in twitch amplitude. Adenosine activated the inwardly rectifying K+ current (IK,Ado), but did not significantly decrease the L-type Ca2+ current (ICa,L). Adenosine reduced the effects of BAY K 8644 on APD90 and twitch amplitude but did not attenuate the BAY K-induced increase in ICa,L. The effects of adenosine on APD90 and twitch amplitude could be reversed after activation of IK,Ado was inhibited by intracellular application of cesium and tetraethylammonium chloride.(ABSTRACT TRUNCATED AT 250 WORDS)
Wang
D
D
Department of Medicine, University of Florida, Gainesville 32610.
Belardinelli
L
L
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D003864:Depression, Chemical; D004553:Electric Conductivity; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D026902:Potassium Channel Blockers; D012044:Regression Analysis; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D002121:Calcium Channel Blockers; D026902:Potassium Channel Blockers; D013757:Tetraethylammonium Compounds; D002104:Cadmium; D002586:Cesium; D019789:Tetraethylammonium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002217:Carbachol; D000241:Adenosine