Author:

Keywords:

Acetylcholine, Adenosine, Adenosine Triphosphate, Aluminum Compounds, Animals, Cells, Cultured, Fluorides, GTP-Binding Proteins, Guanosine 5'-O-(3-Thiotriphosphate), Guinea Pigs, Heart, Heart Ventricles, Kinetics, Potassium Channels, Research Support, Non-U.S. Gov't, Time Factors, Science & Technology, Life Sciences & Biomedicine, Neurosciences, Physiology, Neurosciences & Neurology, POTASSIUM CHANNELS, ACTIVATION, MYOCYTES, MECHANISM, HEART, MODULATION, 06 Biological Sciences, 11 Medical and Health Sciences, 31 Biological sciences, 32 Biomedical and clinical sciences, 42 Health sciences

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.