Muscarinic and Nicotinic ACh Receptor Activation Differentially Mobilize Ca2+in Rat Intracardiac Ganglion Neurons

Abstract

The origin of intracellular Ca2+concentration ([Ca2+]i) transients stimulated by nicotinic (nAChR) and muscarinic (mAChR) receptor activation was investigated in fura-2-loaded neonatal rat intracardiac neurons. ACh evoked [Ca2+]iincreases that were reduced to ∼60% of control in the presence of either atropine (1 μM) or mecamylamine (3 μM) and to <20% in the presence of both antagonists. Removal of external Ca2+reduced ACh-induced responses to 58% of control, which was unchanged in the presence of mecamylamine but reduced to 5% of control by atropine. The nAChR-induced [Ca2+]iresponse was reduced to 50% by 10 μM ryanodine, whereas the mAChR-induced response was unaffected by ryanodine, suggesting that Ca2+release from ryanodine-sensitive Ca2+stores may only contribute to the nAChR-induced [Ca2+]iresponses. Perforated-patch whole cell recording at –60 mV shows that the rise in [Ca2+]iis concomitant with slow outward currents on mAChR activation and with rapid inward currents after nAChR activation. In conclusion, different signaling pathways mediate the rise in [Ca2+]iand membrane currents evoked by ACh binding to nicotinic and muscarinic receptors in rat intracardiac neurons.