Acetylcholine activates nonselective cation channels in guinea pig ileum through a G protein.
Acetylcholine (ACh) depolarizes the membrane of mammalian intestinal myocytes by activating a nonselective cation channel (G. D. Benham, T. B. Bolton, and R. J. Lang. Nature Lond. 316: 345-347, 1985; R. Inoue, K. Kitamura, and H. Kuriyama. Pfluegers Arch. 410: 69-74, 1987). Here, we present evidence that occupation of the muscarinic receptor by ACh couples to channel activation via a G protein; the coupling can be blocked by pertussis toxin or by intracellular guanosine 5'-O-(2-thio-diphosphate) (GDP beta S), whereas intracellular guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) activates the channel in the absence of ACh. The currents, activated by either ACh or GTP gamma S, are nonadditive, conduct sodium ions, and are similar in their voltage dependence and facilitation by submicromolar calcium ions in the cytosol.
Inoue
R
R
Department of Physiology, University of Cologne, Federal Republic of Germany.
Isenberg
G
G
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000031:analogs & derivatives; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D037342:Pertussis Toxin; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007473:Ion Channels; D011976:Receptors, Muscarinic; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; C034883:guanosine 5'-O-(2-thiotriphosphate); D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C023427:guanosine 5'-O-(2-thiodiphosphate); D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000109:Acetylcholine