KINETICS OF G-PROTEIN MEDIATED MODULATION OF THE POTASSIUM M-CURRENT IN BULLFROG SYMPATHETIC NEURONS

The inhibition of the voltage-dependent, K+ M-current (I(M)) 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 I(M) recovery rate following agonist removal was 3-7 min-1. It is proposed that the overall kinetics of the transduction pathway for I(M) modulation is governed by the agonist-dependent kinetics of nucleotide interaction with G proteins. A simple model of I(M) 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 I(M) inhibition in sympathetic neurons.