PERTUSSIS TOXIN AND VOLTAGE DEPENDENCE DISTINGUISH MULTIPLE PATHWAYS MODULATING CALCIUM CHANNELS OF RAT SYMPATHETIC NEURONS

Agonist-induced suppression of current in voltage-gated Ca2+ channels was studied in rat sympathetic neurons. We have previously distinguished two intracellular signaling pathways used by muscarinic agonists to suppress neuronal Ca2+ current-one fast and membrane delimited, the other slow and acting via a diffusible second messenger. We now show that the fast pathway is sensitive mainly to pertussis toxin and shifts the gating of Ca2+ channels to more positive voltages (voltage dependent). The slow pathway is pertussis toxin insensitive and depresses currents at all test potentials (voltage independent). Muscarinic agonists may also activate a pertussis toxin-insensitive fast pathway. Alpha-adrenergic agonists use the fast pertussis toxin-sensitive and the fast insensitive pathways, but not the slow one.