Xanthine affects [Ca2+]i and contractile responses of ventricular cardiocytes to electrical stimulation.
Xanthine, a major purine by-product of ATP, accumulates during myocardial ischemia. In the present study, we show that xanthine (0.5-1 mM) impaired the occurrence of cytosolic Ca2+ concentration ([Ca2+]i) transients, visualized in fura 2-loaded cells, and twitches of contraction in ventricular cardiocytes in response to electrical stimulation. This effect of xanthine was independent of superoxide anion production. That it was a result of decreased membrane excitability was supported by the following: 1) it was reversed by increasing either the amplitude of the stimulus voltage required to stimulate cardiocytes or the extracellular concentration of NaCl; and 2) xanthine reversed the depolarization following electrical stimulation in cardiocytes loaded with the voltage-sensitive dye bis-oxonol. P2 purinergic-agonists, including ATP (10 microM), but not P1 purinergic agonists reproduced the effects seen with xanthine. In addition, a lack of additivity between xanthine and ATP at maximal concentrations was observed. We conclude that xanthine, through activation of a P2 purinoceptor, may contribute to myocardial arrhythmia occurring during ischemia-reperfusion injury.
Rohn
T T
TT
Institut National de la Santé et de la Recherche Médicale Unité 99, Hôpital Henri Mondor, Créteil, France.
Sauvadet
A
A
Pavoine
C
C
Pecker
F
F
D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016764:Cell Polarity; D002478:Cells, Cultured; D002642:Chick Embryo; D003600:Cytosol / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D007700:Kinetics; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D019820:Xanthine; D014970:Xanthines / Q000494:pharmacology*
D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D014970:Xanthines; D013481:Superoxides; D019820:Xanthine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine; D002118:Calcium