Heparin uncouples the muscarinic receptors from GK protein in the atrial cell membrane of the guinea-pig heart.
The effects of heparin on activation of the G protein-gated muscarinic K+ channel were examined in atrial cells of guinea-pig heart. The inside-out patch clamp technique was used. The pipette solution contained 1.1 microM acetylcholine (ACh). In the inside-out patches, intracellular GTP activated the muscarinic, K+ channel. When heparin (0.05-5 units/ml) was further added to the intracellular side of the patch membrane, the channel openings were depressed in a concentration-dependent fashion. The effects of heparin were reversible after wash-out. Heparin did not affect GTP-gamma S-induced activation of the K+ channel. Therefore, it is suggested that heparin may uncouple the muscarinic receptors from GK protein in the cardiac atrial cell membrane.
Ito
H
H
2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Takikawa
R
R
Iguchi
M
M
Hamada
E
E
Sugimoto
T
T
Kurachi
Y
Y
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D006168:Guinea Pigs; D006325:Heart Atria / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D006493:Heparin / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism
D015221:Potassium Channels; D011976:Receptors, Muscarinic; D006493:Heparin; D019204:GTP-Binding Proteins