AN ATP-ACTIVATED NONSELECTIVE CATION CHANNEL IN GUINEA-PIG VENTRICULAR MYOCYTES

Extracellular ATP released from nerves onto vascular smooth muscle or released from damaged tissues during traumatic injury, shock, or ische mia profoundly alters cardiovascular physiology. We have used patch-cl amp 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 ac tivates a rapid, desensitizing, inward current. This inward current is activated by a P-2 receptor that does not conform to published recept or subclasses. A concentration of 100 mu M ATP activates more current than 100 mu M alpha/beta-methyleneadenosine 5'-triphosphate, which in turn activates more current than 100 mu M ADP. 2-Methylthioadenosine 5 '-triphosphate (2-MeS-ATP) and adenosine 5'-O-(3-thiotriphosphate) are also effective agonists. Adenosine, AMP, guanosine 5'-triphosphate, a nd uridine 5'-triphosphate are ineffective at 100 mu M. The inward con ductance has a reversal potential near 0 mV and in ion-substitution ex periments was found to be carried through nonselective cation channels rather than chloride channels. The conductance has inwardly rectifyin g current-voltage (I-V) relations. When ATP is used as the agonist, fl uctuation analysis yields an apparent unitary conductance of 0.08 pA a t a holding potential of - 120 mV with sodium as the main charge-carry ing ion. The combination of inwardly rectifying I-V relations, the eff icacy of 2-MeS-ATP, and the very low conductance distinguish this cond uctance from other ATP-activated nonselective channels, including thos e recently cloned from rat vas deferens and PC-12 cells.