Mode of regulation by G protein of the ATP-sensitive K+ channel in guinea-pig ventricular cell membrane

• Published in: The Journal of physiology Vol. 478; no. Pt 1; pp. 101 - 107
• Main Authors: Ito, H, Vereecke, J, Carmeliet, E
• Format: Journal Article
• Language: English
• Published: England The Physiological Society 01.07.1994
• Subjects: Acetylcholine - pharmacology; Adenosine - pharmacology; Adenosine Triphosphate - pharmacology; Aluminum Compounds - pharmacology; Animals; Cells, Cultured; Fluorides - pharmacology; GTP-Binding Proteins - physiology; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology; Guinea Pigs; Heart - physiology; Heart Ventricles; Kinetics; Potassium Channels - drug effects; Potassium Channels - physiology; Time Factors
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.1994.sp020233

1. The effect of G protein activation on the ATP-sensitive K+ (K+ATP) channel was examined in inside-out patches from guinea-pig ventricular myocytes. At low (0.3 mM) intracellular ATP concentration ([ATP]i) in the bathing solution, in the absence of agonists in the pipette, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) or AlF4- applied to the intracellular side of the patch membrane gradually activated the K+ATP channel. The activation by GTP gamma S was irreversible, although high [ATP]i could completely close the channel. 2. In ATP-free media GTP gamma S did not increase further the activity of the fully active channel, and was unable to reactivate the channel in the non-operative state after rundown. [ATP]i-channel activity curves constructed before and after GTP gamma S application demonstrated that GTP gamma S shifts the half-inhibitory [ATP]i from 19.5 to 110 microM without changing the Hill coefficient. 3. When acetylcholine or adenosine was included in the pipette, intracellular GTP reversibly activated the K+ATP channel which was partially inhibited by [ATP]i. 4. These results indicate that G protein may stimulate myocardial K+ATP channels in the operative state by reducing the potency of ATP inhibition. The possible coupling of the G protein with muscarinic as well as A1 adenosine receptors is suggested.