Selective attenuation by adenosine of arrhythmogenic action of isoproterenol on ventricular myocytes

Citation
Yj. Song et al., Selective attenuation by adenosine of arrhythmogenic action of isoproterenol on ventricular myocytes, AM J P-HEAR, 280(6), 2001, pp. H2789-H2795
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
ISSN journal
0363-6135 → ACNP
Volume
280
Issue
6
Year of publication
2001
Pages
H2789 - H2795
Database
ISI
SICI code
0363-6135(200106)280:6<H2789:SABAOA>2.0.ZU;2-E
Abstract
We examined whether adenosine equally attenuated the stimulatory effects of isoproterenol on arrhythmic activity and twitch shortening of guinea pig i solated ventricular myocytes. Transmembrane voltages and whole cell current s were recorded with patch electrodes, and cell twitch shortening was measu red using a video-motion detector. Isoproterenol increased the action poten tial duration at 50% repolarization (APD(50)), L-type Ca2+ current [I-Ca(L) ], and cell twitch shortening and induced delayed afterdepolarizations (DAD ), transient inward current (I-Ti), and aftercontractions. Adenosine attenu ated the arrhythmogenic actions of isoproterenol more than it attenuated th e effects of isoproterenol on APD(50), I-Ca(L), or twitch shortening. Adeno sine (0.1-100 mu mol/l) decreased the amplitude of DADs by 30 +/- 6% to 92/- 5% but attenuated isoproterenol-induced prolongation of the APD(50) by o nly 14 +/- 4% to 59 +/- 4% and had no effect on the voltage of action poten tial plateau. Adenosine (30 mu mol/l) inhibited I-Ti by 91 +/- 4% but decre ased isoproterenol-stimulated I-Ca(L) by only 30 +/- 12%. Isoproterenol-ind uced aftercontractions were abolished by adenosine (10 mu mol/l), whereas t he amplitude of twitch shortening was not reduced. The effects of adenosine on twitch shortenings and aftercontractions were mimicked by the A(1)-aden osine receptor agonist CPA (N-6-cyclopentyladenosine) and by ryanodine. In conclusion, adenosine antagonized the proarrhythmic effect of beta -adrener gic stimulation on ventricular myocytes without reducing cell twitch shorte ning.