ACETYLCHOLINE-RECEPTORS IN RAT CARDIAC NEURONS

Membrane potential changes produced by acetylcholine (ACh), and their underlying mechanisms, were studied in neurones of isolated cardiac ganglia of the rat by means of intracellular microelectrodes. Five components of membrane potential change could be detected in cardiac neurones following 1-5 s micro-application of ACh: (i) fast depolarization resulting from an activation of nonselective cationic conductance; (ii) slow depolarization associated with a decreased membrane conductance, presumably for potassium ions; slow hyperpolarization which consisted of (iii) early and (iv) late parts resulting from an activation of calcium-sensitive potassium current and from inhibition of steady-state inward current, respectively; and (v) delayed slow hyperpolarization associated with an increased conductance, most likely for potassium ions. Components (i), (iii) and (iv) persisted in the presence of atropine and were inhibited by nicotinic antagonists. Thus they were due to activation of nicotinic ACh receptors. However, the sensitivity of component (i) to ganglion-blocking agents appeared to be rather low: IC50s for inhibiting (i) were 226 +/- 34.2-mu-M, 31.2 +/- 4.31-mu-M and 15.3 +/- 3.27-mu-M for hexamethonium, d-tubocurarine, and trimetaphan, respectively. Components (ii) and (v) were abolished by atropine (1-mu-M) and mimicked by muscarine (component (ii) also persisted in d-tubocurarine), hence they resulted from activation of muscarinic ACh receptors. It is concluded that cardiac neurones are endowed with both nicotinic and muscarinic ACh receptors. Their activation leads to membrane depolarization and discharges followed by hyperpolarization and inhibition of discharges.