Short-term desensitization of muscarinic K+ channel current in isolated atrial myocytes and possible role of GTP-binding proteins.
The short-term desensitization of the acetylcholine (ACh)-induced K+ channel current was examined in single atrial cells of guinea-pig heart. The tight-seal whole cell voltage clamp technique was used. The solution in the pipettes contained GTP or guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma S, a non-hydrolyzable GTP analogue). In GTP-loaded cells, ACh evoked a specific K+ channel current via GTP-binding proteins (G) in a dose-dependent manner. The K+ current showed agonist-dependent desensitization similar to those reported in other cardiac tissues (Nilius 1983; Carmeliet and Mubagwa 1986). The cellular response to ACh was also desensitized by activation of P1-purinergic receptors with adenosine (Ado). In GTP-gamma S-loaded cells, the K+ current was gradually induced even in the absence of agonists, probably due to direct activation of G proteins by GTP-gamma S. In the early phase of the spontaneous current increase, ACh evoked a large current transiently. As the GTP-gamma S-induced activation of the current progressed, the magnitude of the ACh-evoked current transient became smaller and finally negligible. Similar results were obtained when Ado was used as an agonist instead of ACh to induce the K+ current. Therefore, it is indicated that the agonist-receptor interaction may not be essential for the desensitization of ACh-induced K+ current in atrial myocytes.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D016275:Atrial Function; D004361:Drug Tolerance; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D011188:Potassium / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology
D007473:Ion Channels; D011976:Receptors, Muscarinic; D013873:Thionucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D000109:Acetylcholine; D011188:Potassium