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 chick ciliary ganglion neurons have three classes of receptors activated by the same neurotransmitter, acetylcholine, and that all three regulate the same second messenger, intracellular free calcium. Activation of muscarinic receptors on the neurons stimulates phosphatidylinositol turnover and induces calcium oscillations that are initiated and maintained by calcium release from caffeine/ryanodine-insensitive intracellular stores. Extracellular calcium is required to sustain the oscillations, while cadmium abolishes them. Activation of either of two classes of nicotinic receptors, distinguished both by location on the neurons and by subunit composition, induces a single, rapid elevation in intracellular calcium without inducing phosphatidylinositol turnover. The nicotinic responses are entirely dependent on extracellular calcium, show no dependence on release from internal stores, and do not display oscillations. Low concentrations of the native agonist, acetylcholine, induce repetitive calcium spikes in the neurons characteristic of muscarinic receptors, while higher concentrations induce nonoscillating increases in intracellular calcium that include contributions from nicotinic receptors. The three classes of receptors also differ in the acetylcholine concentration required to elicit a response. These differences, together with differences in receptor location and sources of calcium mobilized, may enable the receptor subtypes to target different sets of calcium-dependent processes for regulation.