CHARACTERIZATION OF FUNCTIONAL ANTAGONISM OF ADENOSINE AND ISOPROTERENOL IN GUINEA-PIG ATRIAL MYOCYTES

The role of adenosine action in modulating the action potential duration (APD) of single isolated guinea-pig atrial myocytes during beta-adrenergic stimulation with isoproterenol was investigated. Membrane potential and ionic currents were measured by the tight-seal, whole-cell patch-clamp technique. Adenosine (10 muM) antagonized isoproterenol (20 nm)-stimulated L-type calcium inward current (I(ca)). In the presence of isoproterenol, adenosine (10 mum) also increased holding and late outward currents. Isoproterenol (20 nM) caused a significant prolongation in atrial action potential at the level of 0 mV, rather than at 90% repolarization. Adenosine shortened atrial action potential dose-dependently in the presence of isoproterenol. The respective values for EC50 and maximally shortened action potential duration at 0 mV of adenosine with or without isoproterenol (20 nm) were 3.0 vs. 2.2 mum and 42.9 vs. 30.4 ms. In summary, during beta-adrenergic stimulation with isoproterenol, in guinea-pig atrial myocytes, adenosine elicited the specific K+-outward current and concomitantly attenuated the isoproterenol-stimulated I(Ca). These phenomena may account for the modulation of atrial action potenital by adenosine with or without isoproterenol effect.