Heparin uncouples the muscarinic receptors from GK protein in the atrial cell membrane of the guinea-pig heart.

The effects of heparin on activation of the G protein-gated muscarinic K+ channel were examined in atrial cells of guinea-pig heart. The inside-out patch clamp technique was used. The pipette solution contained 1.1 microM acetylcholine (ACh). In the inside-out patches, intracellular GTP activated the muscarinic, K+ channel. When heparin (0.05-5 units/ml) was further added to the intracellular side of the patch membrane, the channel openings were depressed in a concentration-dependent fashion. The effects of heparin were reversible after wash-out. Heparin did not affect GTP-gamma S-induced activation of the K+ channel. Therefore, it is suggested that heparin may uncouple the muscarinic receptors from GK protein in the cardiac atrial cell membrane.