title: An ATP-activated nonselective cation channel in guinea pig ventricular myocytes.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4970, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Parker
authors.forename: A
authors.initials: A
authors.lastname: Scarpa
mesh_terms: 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
chemical_list: D002412:Cations; D007473:Ion Channels; D058913:Purinergic Agonists; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate