Selective attenuation by adenosine of arrhythmogenic action of isoproterenol on ventricular myocytes.
We examined whether adenosine equally attenuated the stimulatory effects of isoproterenol on arrhythmic activity and twitch shortening of guinea pig isolated ventricular myocytes. Transmembrane voltages and whole cell currents were recorded with patch electrodes, and cell twitch shortening was measured using a video-motion detector. Isoproterenol increased the action potential duration at 50% repolarization (APD50), L-type Ca2+ current [I(Ca(L))], and cell twitch shortening and induced delayed afterdepolarizations (DAD), transient inward current (I(Ti)), and aftercontractions. Adenosine attenuated the arrhythmogenic actions of isoproterenol more than it attenuated the effects of isoproterenol on APD50, I(Ca(L)), or twitch shortening. Adenosine (0.1-100 micromol/l) decreased the amplitude of DADs by 30 +/- 6% to 92 +/- 5% but attenuated isoproterenol-induced prolongation of the APD50 by only 14 +/- 4% to 59 +/- 4% and had no effect on the voltage of action potential plateau. Adenosine (30 micromol/l) inhibited I(Ti) by 91 +/- 4% but decreased isoproterenol-stimulated I(Ca(L)) by only 30 +/- 12%. Isoproterenol-induced aftercontractions were abolished by adenosine (10 micromol/l), whereas the amplitude of twitch shortening was not reduced. The effects of adenosine on twitch shortenings and aftercontractions were mimicked by the A1-adenosine receptor agonist CPA (N6-cyclopentyladenosine) and by ryanodine. In conclusion, adenosine antagonized the proarrhythmic effect of beta-adrenergic stimulation on ventricular myocytes without reducing cell twitch shortening.
Song
Y
Y
Department of Medicine, University of Florida, Gainesville, Florida 32610, USA.
Shryock
J C
JC
Knot
H J
HJ
Belardinelli
L
L
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002469:Cell Separation; D004336:Drug Antagonism; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018715:Microscopy, Video; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D058906:Purinergic P1 Receptor Agonists; D012433:Ryanodine / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D020746:Calcium Channels, L-Type; D002316:Cardiotonic Agents; D058906:Purinergic P1 Receptor Agonists; D012433:Ryanodine; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine; D007545:Isoproterenol