APStracts 2:0126H, 1995.

An atp-activated nonselective cation channel in guinea pig ventricular myocytes. Parker, Karen E., and Antonio Scarpa. Case Western Reserve University School of Medicine, Department of Physiology and Biophysics, Cleveland, OH 44106-4970

APStracts 2:0126H, 1995.

Extracellular ATP released from nerves onto vascular smooth muscle or released from damaged tissues during traumatic injury, shock or ischemia profoundly alters cardiovascular physiology. We have used patch-clamp methods to investigate the effects of extracellular ATP on guinea pig ventricular myocytes because guinea pigs are a commonly used model for the study of cardiac electrophysiology. We have found that ATP activates a rapid, desensitizing, inward current. This inward current is activated by a P2 receptor that does not conform to published receptor sub-classes. 100 uM ATP activates more current than 100 uM alpha-beta-methylene ATP, which in turn activates more current than 100 uM ADP. 2-methylthio ATP and ATP-gamma-S are also effective agonists. Adenosine, AMP, GTP and UTP are ineffective at 100 uM. The inward conductance has a reversal potential near 0 mV and in ion-substitution experiments was found to be carried through nonselective cation channels rather than chloride channels. The conductance has inwardly rectifying current-voltage relations. When ATP is used as the agonist, fluctuation analysis yields an apparent unitary conductance of 0.08 pA at a holding potential of -120 mV with sodium as the main charge-carrying ion. The combination of inwardly -rectifying I/V relations, the efficacy of 2-methylthio ATP, and the very low conductance distinguish this conductance from other ATP -activated non-selective channels, including those recently cloned from rat vas deferens and PC-12 cells.

Received 1 December 1994; accepted in final form 10 March 1995.
APS Manuscript Number H1053-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 April 1995.