[Action of AMP579 and adenosine on potassium or sodium ionic channels in isolated rat and guinea pig ventricular myocytes].
OBJECTIVE
To study the effect of AMP579 and adenosine on potassium ionic (K+) or sodium ionic (Na+) channels and to elucidate ionic mechanisms underlying negative inotropic and antiarrhythmic effects of AMP579 and adenosine.


METHODS
Ionic channel currents of rat and guinea pig ventricular myocytes were recorded by patch clamp technique in whole-cell configuration.


RESULTS
Adenosine showed a stronger activating effect on transient outward K+ current (I(to)) than AMP579, EC50 of adenosine and AMP579 were 2.33 and 8. 32 micromol x L(-1), respectively (P < 0.05). An adenosine A1 receptor blocker, 1,3-dipropyl-8-cyclopentylxanthine (PD116948), can abolish the effects of AMP579 and adenosine on I(to), demonstrating that the effect is mediated by adenosine A1 receptor. Adenosine exerted a more obvious inhibitory effect on delayed rectifier K+ current (IK) than AMP579. IC50 of adenosine and AMP579 were 1.21 and 2.31 micromol x L(-1), respectively (P < 0.05). AMP579 had a more powerful inhibitory effect on inward rectifier K+ current (IK1) than adenosine. IC50 of AMP579 and adenosine were 4.15 and 20.7 micromol x L(-1), repectively (P < 0.01). AMP579 and adenosine exerted a similar inhibitory effect on fast inward Na+ current (INA), IC50 of AMP579 and adenosine were 9.46 and 6.23 micromol x L(-1), respectively (P > 0.05).


CONCLUSIONS
Adenosine showed a stronger activating effect on I(to) than AMP579, however, the mechanism of AMP579 and adenosine activating I(to) was mediated by adenosine A1 receptor. AMP579 has a more powerful inhibitory effect on IK1, and less inhibitory effect on IK than adenosine. Both drugs have a similar inhibitory effect on INa. The negative inotropic and antiarrhythmic effects are related to these ionic mechanisms.
Wang
Xiong
X
Department of Cardiology, First Hospital, Shanxi Medical University, Taiyuan 030001, China. wxiong@public.ty.sx.cn
Wu
Bo-wei
BW
Wu
Dong-mei
DM
D000241:Adenosine / Q000737:chemistry / Q000494:pharmacology*; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D015394:Molecular Structure; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000502:physiology*; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
C113971:4-(7-((2-3-chloro-2-thienyl)-1-methyl-propylamino)-3H-imidazo(4,5-b)pyridyl-3-yl)cyclopentane carboxamide; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D007093:Imidazoles; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011725:Pyridines; D015222:Sodium Channels; D014970:Xanthines; C057837:3,7-dimethyl-1-propargylxanthine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D013805:Theobromine