Tt. Rohn et al., XANTHINE AFFECTS [CA2-STIMULATION(](I) AND CONTRACTILE RESPONSES OF VENTRICULAR CARDIOCYTES TO ELECTRICAL), American journal of physiology. Cell physiology, 42(3), 1997, pp. 909-917
Xanthine, a major purine by-product of ATP, accumulates during myocard
ial ischemia. In the present study, we show that xanthine (0.5-1 mM) i
mpaired the occurrence of cytosolic Ca2+ concentration ([Ca2+](i)) tra
nsients, visualized in fura 2-loaded cells, and twitches of contractio
n in ventricular cardiocytes in response to electrical stimulation. Th
is effect of xanthine was independent of superoxide anion production.
That it was a result of decreased membrane excitability was supported
by the following: I)it was reversed by increasing either the amplitude
of the stimulus voltage required to stimulate cardiocytes or the extr
acellular concentration of NaCl; and 2) xanthine reversed the depolari
zation following electrical stimulation in cardiocytes loaded. with th
e voltage-sensitive dye bis-oxonol. P-2 purinergic-agonists, including
ATP (10 mu M), but not P-1 purinergic agonists reproduced the effects
seen with xanthine. In addition, a lack of additivity between xanthin
e and ATP at maximal concentrations was observed. We conclude that xan
thine, through activation of a Pg purinoceptor, may contribute to myoc
ardial arrhythmia occurring during ischemia-reperfusion injury.