Effects of halothane on the sympathetic nerve terminals of the rabbit heart. Differences in membrane actions of halothane and tetracaine.

Abstract

1. The isolated rabbit heart perfused with Tyrode solution at constant flow was used to investigate the noradrenaline output from the sympathetic nerve terminals. The noradrenaline concentration in the perfusate was measured spectrofluorimetrically. 2. The spontaneous noradrenaline output and the noradrenaline release evoked by submaximal electrical stimulation of the postganglionic sympathetic nerves were not influenced by halothane at concentrations of 7.5×10−5 or 2.24×10−4 g/ml. 3. The noradrenaline release evoked by 1,1-dimethyl-4-phenylpiperazine or by acetylcholine (in the presence of atropine) was decreased by halothane. This decrease was concentration-dependent and the halothane concentration causing 50% inhibition amounted to 6×10−5 g/ml. The threshold concentration of halothane which induced significant decrease in noradrenaline output was 1/3 to 1/10 of that which caused significant reduction in heart rate or contractility. 4. Halothane (7.5×10−5 or 2.24×10−4 g/ml) did not affect the noradrenaline output evoked by raising the concentration of KCl in the perfusion fluid by 150 mM. 5. Tetracaine (2.6×10−8 to 2.6×10−5 g/ml) did not alter the noradrenaline release evoked by raising the concentration of KCl in the perfusion fluid by 50, 80 and 150 mM, respectively. 6. The amount of exogenous noradrenaline removed from the Tyrode solution during passage through the heart was not altered by halothane (2.24×10−5 to 7.5×10−4 g/ml). 7. The results indicate that the inhibitory effect of halothane on the noradrenaline output evoked by activation of nicotinic receptors is neither due to an impairment of the process of transmitter release itself nor to a decrease in calcium or sodium permeability of the plasma membrane. Hence, the mechanism of action of halothane is different from that of tetracaine which, in the terminal and/or preterminal parts of the sympathetic nerves, predominantly blocks sodium conductance of the plasma membrane. Halothane may inhibit stimulus formation by inducing a conformational change of receptor proteins which may prevent the interaction of agonists with the nicotinic receptor.