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. 1994 Jul 1;478(Pt 1):101–107. doi: 10.1113/jphysiol.1994.sp020233

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

H Ito 1, J Vereecke 1, E Carmeliet 1
PMCID: PMC1155648  PMID: 7965825

Abstract

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.

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Selected References

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