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Am J Physiol Cell Physiol 264: C1411-C1417, 1993;
0363-6143/93 $5.00
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AJP - Cell Physiology, Vol 264, Issue 6 C1411-C1417, Copyright © 1993 by American Physiological Society


ARTICLES

Modulation by extracellular ATP of two distinct currents in rat myocytes

J. S. Zheng, A. Christie, M. N. Levy and A. Scarpa
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.

The whole cell voltage-clamp technique was used to study the electrophysiological effects induced by ATP in isolated ventricular myocytes. ATP or 2-methylthio-ATP evoked a transient inward current (IATP) when the transmembrane potential (Vm) was held at -70 mV and increased the Ca2+ current (ICa) when Vm was depolarized to 0 mV. The time course of IATP was fitted by a single exponential equation with a brief time constant (165 ms), whereas the time course of enhancement of ICa by ATP was also fitted by a single exponential equation with a much longer time constant (14 s). IATP was much less pronounced when extracellular Mg2+ was absent, and it was insensitive to dihydropyridines. In contrast, the enhancement of ICa by ATP was not affected by removing extracellular Mg2+, but it was suppressed by Ca2+ channel blockers. Both IATP and ICa were decreased by extracellular Cd2+. Internally applied guanosine 5'-O-(2-thiodiphosphate), which prevents the activation of G proteins, abolished the ATP-enhanced rise in ICa but did not inhibit IATP. These data suggest that ATP elicits IATP and increases ICa through two different mechanisms. IATP appears to be generated via receptor-operated channels that are activated by ATP. The ATP-induced increase of ICa appears to be mediated by G proteins via pathways that are independent of adenosine 3',5'-cyclic monophosphate and phosphoinositide turnover.


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