Mode of regulation by G protein of the ATP-sensitive K+ channel in guinea-pig ventricular cell membrane.
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.
Ito
H
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Laboratorium voor Fysiologie, Katholieke Universiteit Leuven, Belgium.
Vereecke
J
J
Carmeliet
E
E
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D005459:Fluorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles; D007700:Kinetics; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D017607:Aluminum Compounds; D015221:Potassium Channels; C050992:tetrafluoroaluminate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000255:Adenosine Triphosphate; D019204:GTP-Binding Proteins; D000241:Adenosine; D000109:Acetylcholine; D005459:Fluorides