SYNERGISTIC REGULATION OF A NEURONAL CHLORIDE CURRENT BY INTRACELLULAR CALCIUM AND MUSCARINIC RECEPTOR ACTIVATION - A ROLE FOR PROTEIN-KINASE-C

Using perforated patch recordings in combination with intracellular Ca2+ ([Ca2+](i)) fluorescence measurements, we have identified a delayed Ca2+-dependent Cl- current in a mammalian sympathetic ganglion cell. This Cl- current is induced by the synergistic action of Ca2+ and diacylglycerol (DAG) and is blocked by inhibitors of protein kinase C. As a result, the current can be induced by acetylcholine through the conjoint activation of nicotinic receptors (to produce a rise in [Ca2+](i)) and muscarinic receptors (to generate DAG). This demonstrates an unusual form of synergism between the two effects of a single transmitter mediated via separate receptors operating within a time scale that could be of physiological significance.