title: Acetylcholine and adenosine activate the G protein-gated muscarinic K+ channel in ferret ventricular myocytes.
abstract: The properties of the K+ channel activated by acetylcholine (ACh) and adenosine (Ado) were examined in single ferret ventricular myocytes using patch-clamp techniques. In the whole-cell configuration, ACh and Ado induced an inwardly rectifying K+ current and shortened the action potential duration. The effect of ACh was blocked by atropine, while the Ado effect was interrupted by 8-cyclopentyl,1,2-dipropyl xanthine, a specific Ado A1 receptor antagonist. In cell-attached recordings, ACh and Ado added to the pipette solution activated a single population of inwardly rectifying K+ channels, distinct from the iK1 channel. The channel had a slope conductance of approximately 40 pS in symmetrical 150 mM K+ solutions and a mean open time of 0.8 ms. Excision of the patch into the inside-out patch configuration in guanosine triphosphate (GTP)-free solution abolished the channel activity. The channel was reversibly reactivated by adding GTP to the intracellular side of the patch. GTP gamma S activated the channel irreversibly. When the inside-out patch was treated with the A protomer of pertussis toxin (PTX), intracellular GTP no longer activated the K+ channel. The results show that ferret ventricular myocytes possess a K+ channel activated by both muscarinic and Ado A1 receptors. Its electrophysiological properties and the gating by a PTX-sensitive G protein in a membrane-delimited fashion are identical with those of the muscarinic K+ channels in nodal and atrial tissues of other species. In conclusion, the G protein-gated muscarinic K+ channel is expressed in ferret ventricular myocardium and may underlie the direct negative inotropism of ACh and Ado in this tissue.
authors.affiliation: Department of Cell Biology and Signaling, Yamagata University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Hosoya
authors.forename: A
authors.initials: A
authors.lastname: Inanobe
authors.forename: H
authors.initials: H
authors.lastname: Tomoike
authors.forename: M
authors.initials: M
authors.lastname: Endoh
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005289:Ferrets; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008297:Male; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015221:Potassium Channels; D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins; D000241:Adenosine; D000109:Acetylcholine