Kinetics of G protein-mediated modulation of the potassium M-current in bullfrog sympathetic neurons.

The inhibition of the voltage-dependent, K+ M-current (IM) following receptor-independent G protein activation with controlled intracellular perfusion of nonhydrolyzable GTP analogs had an exponential time course, with rates hyperbolically dependent on GTP analog concentration, and a limiting value of 0.53 min-1. The inhibitory agonist muscarine caused a concentration-dependent acceleration of the rate of nucleotide-induced inhibition, with a plateau of about 20 min-1 and an exponential time course. In neurons not treated with nucleotide analogs the IM recovery rate following agonist removal was 3-7 min-1. It is proposed that the overall kinetics of the transduction pathway for IM modulation is governed by the agonist-dependent kinetics of nucleotide interaction with G proteins. A simple model of IM modulation based on G proteins' kinetics has been developed. These data suggest a possible cellular process responsible for the time course of slow synaptic potentials caused by IM inhibition in sympathetic neurons.