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 microM) antagonized isoproterenol (20 nM)-stimulated L-type calcium inward current (ICa). In the presence of isoproterenol, adenosine (10 microM) 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 microM 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 ICa. These phenomena may account for the modulation of atrial action potential by adenosine with or without isoproterenol effect.
Wu
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Department of Physiology, Kaohsiung Medical College, Taiwan, R.O.C.
Yu
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HS
D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D016275:Atrial Function; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects
D000241:Adenosine; D007545:Isoproterenol