AJP - Cell Physiology, Vol 273, Issue 3 C909-C917, Copyright © 1997 by American Physiological Society
Xanthine affects [Ca2+]i and contractile responses of ventricular cardiocytes to electrical stimulation
T. T. Rohn, A. Sauvadet, C. Pavoine and F. Pecker
Institut National de la Sante et de la Recherche Medicale Unite 99, Hopital Henri Mondor, Creteil, France.
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.
