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 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 subclasses. A concentration of 100 microM ATP activates more current than 100 microM alpha, beta-methyleneadenosine 5'-triphosphate, which in turn activates more current than 100 microM ADP. 2-Methylthioadenosine 5'-triphosphate (2-MeS-ATP) and adenosine 5'-O-(3-thiotriphosphate) are also effective agonists. Adenosine, AMP, guanosine 5'-triphosphate, and uridine 5'-triphosphate are ineffective at 100 microM. 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 (I-V) 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-MeS-ATP, and the very low conductance distinguish this conductance from other ATP-activated nonselective channels, including those recently cloned from rat vas deferens and PC-12 cells.
Parker
K E
KE
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4970, USA.
Scarpa
A
A
D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002412:Cations / Q000378:metabolism*; D004553:Electric Conductivity; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D006352:Heart Ventricles; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D058913:Purinergic Agonists; D011983:Receptors, Purinergic / Q000187:drug effects / Q000378:metabolism
D002412:Cations; D007473:Ion Channels; D058913:Purinergic Agonists; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate