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Mode of regulation by G protein of the ATP‐sensitive K+ channel in guinea‐pig ventricular cell membrane.
Author(s) -
Ito H,
Vereecke J,
Carmeliet E
Publication year - 1994
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1994.sp020233
Subject(s) - gtp' , biophysics , g protein , intracellular , chemistry , guanosine , membrane potential , adenosine triphosphate , adenosine , biochemistry , biology , receptor , enzyme
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.