An electrophysiological study on the anti-ventricular arrhythmic effect of adenosine in the guinea pig.
- Author:
Zheng-Hang ZHAO
1
;
Wei-Jin ZANG
;
Xiao-Jiang YU
;
Yi-Min ZANG
Author Information
1. Department of Pharmacology, School of Medicine, Xi an Jiaotong University, Xi an 710061.
- Publication Type:Journal Article
- MeSH:
Action Potentials;
drug effects;
Adenosine;
pharmacology;
Animals;
Anti-Arrhythmia Agents;
pharmacology;
Arrhythmias, Cardiac;
physiopathology;
Calcium Channels, L-Type;
drug effects;
Female;
Guinea Pigs;
Heart Ventricles;
cytology;
Isoproterenol;
antagonists & inhibitors;
Male;
Myocytes, Cardiac;
physiology;
Patch-Clamp Techniques
- From:
Acta Physiologica Sinica
2003;55(1):36-41
- CountryChina
- Language:English
-
Abstract:
Using whole-cell patch clamp technique this study investigated the effects of adenosine (Ado) on action potential, L-type calcium current (I(Ca.L)), delayed afterdepolarizations (DADs), and transient inward current (I(ti)) induced by isoproterenol (Iso) in guinea pig isolated single ventricular myocytes. The results showed: (1) Ado alone had no significant direct effects on action potential and I(Ca.L) in guinea pig ventricular myocytes at 20-100 micromol/L. However, Ado significantly attenuated the prolongation of action potential duration (APD) and the increase of the peak amplitude of I(Ca.L) induced by Iso. Iso (10 nmol/L) markedly increased APD(50) and APD(90) from 340+/-21 ms to 486+/-28 ms and from 361+/-17 ms to 501+/-29 ms, respectively (P<0.01), and increased the amplitude of I(Ca.L) from 6.53+/-1.4 pA/pF to 18.28+/-2.4 pA/pF (P<0.01). The peak potential of current-potential relationship shifted to the left. Ado (50 micromol/L) abbreviated APD(50), APD(90) to 403+/-19 ms and 419+/-26 ms (P<0.01), and decreased the peak amplitude of I(Ca.L) to 10.2+/-1.5 pA/pF (P<0.01 vs Iso), but did not change resting membrane potential (RMP), action potential amplitude (APA), and overshoot (OS). (2) Iso (30 nmol/L) reproducibly elicited DADs with 100% incidence of DADs under this condition. Ado (50 micromol/L) completely inhibited Iso from inducing DADs. Iso (30 nmol/L) elicited I(ti) with 2-second depolarizing voltage-clamp pulses rising to +20 mV from a holding potential of -40 mV, the incidence of I(ti) being 100%, and the I(ti) was suppressed in the presence of Ado (50 micromol/L) with the incidence of I(ti) decreased to 14.3% (P<0.05). These data indicate that Ado antagonizes the stimulatory effect of Iso, and that the antiarrhythmic mechanism of Ado preventing Iso-induced DADs is due to the inhibition of intracellular Ca(2+) overload through attenuating the prolongation of APD, the enhance of I(Ca.L) and I(ti).
