ACETYLCHOLINE DIFFERENTIALLY AFFECTS INTRACELLULAR CALCIUM VIA NICOTINIC AND MUSCARINIC RECEPTORS ON THE SAME POPULATION OF NEURONS

Multiple receptor subtypes activated by the same ligand but coupled to different second messengers can produce divergent signaling in a cell , while receptors activated by different ligands but sharing the same second messenger can produce convergent signaling, We show here that c hick ciliary ganglion neurons have three classes of receptors activate d by the same neurotransmitter, acetylcholine, and that all three regu late the same second messenger, intracellular free calcium, Activation of muscarinic receptors on the neurons stimulates phosphatidylinosito l turnover and induces calcium oscillations that are initiated and mai ntained by calcium release from caffeine/ryanodine-insensitive intrace llular stores, Extracellular calcium is required to sustain the oscill ations, while cadmium abolishes them, Activation of either of two clas ses of nicotinic receptors, distinguished both by location on the neur ons and by subunit composition, induces a single, rapid elevation in i ntracellular calcium without inducing phosphatidylinositol turnover, T he nicotinic responses are entirely dependent on extracellular calcium , show no dependence on release from internal stores, and do not displ ay oscillations, Low concentrations of the native agonist, acetylcholi ne, induce repetitive calcium spikes in the neurons characteristic of muscarinic receptors, while higher concentrations induce nonoscillatin g increases in intracellular calcium that include contributions from n icotinic receptors, The three classes of receptors also differ in the acetylcholine concentration required to elicit a response. These diffe rences, together with differences in receptor location and sources of calcium mobilized, may enable the receptor subtypes to target differen t sets of calcium-dependent processes for regulation.