GTP-binding proteins mediate the M2-muscarinic effect on the action potential in isolated sympathetic neurons of rabbits.

Activation of M2-muscarinic receptors alters the configuration of the action potential due to depression of the calcium-dependent components, the shoulder in the falling phase and the afterhyperpolarization, in isolated superior cervical ganglionic neurons of rabbits. This effect was inhibited by preincubation of the cells with pertussis toxin, or by the intracellular administration of guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S). The muscarinic effect persisted in the cells loaded with guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S). Intracellular application of cAMP and 3-isobutyl-l-methylxanthine did not change the muscarinic effect. The results suggest that a GTP-binding protein is involved in the cAMP-independent, M2-muscarinic receptor-mediated regulation of action potential firing in sympathetic neurons.