Differential effects of the muscarinic M 2 antagonists, AF-DX 116 and gallamine, on single neurons of rabbit sympathetic ganglia

Abstract

Intracellular recording techniques were used to compare the effects of the M 2 muscarinic antagonists, AF-DX 116 and gallamine, on membrane potential ( V m), input resistance ( R i), responses induced by methacholine, muscarinic slow postsynaptic potentials and action potentials in the superior cervical ganglion of the rabbit. Gallamine or AF-DX 116 antagonized methacholine-induced or synaptically-evoked muscarinic hyperpolarization, without having significant effect on depolarization induced by methacholine or synaptically. The drug AF-DX 116 reduced evoked muscarinic hyperpolarizing potentials, without significant change in V m or R i, recorded in the absence of muscarinic stimulation. In contrast to AF-DX 116, gallamine elicited a concentration-dependent depolarization of the membrane, with a corresponding increase in R i, when tested in the absence of muscarinic stimulation. These effects of gallamine were accompanied by an increase in duration and decrease in the slope of the descending phase of the action potential. Blockade by gallamine of evoked hyperpolarization was independent of membrane depolarization and readily occurred when gallamine-induced depolarization was prevented by clamping V m at its pre-gallamine level. The effects of gallamine were maintained during its presence and reversed upon washing with gallamine-free physiological solution. These results indicate that AF-DX 116 and gallamine have a specificity for antagonism of muscarinic responses, mediated by receptors of the M 2 type in the superior cervical ganglion. However, gallamine, while an effective antagonist of M 2 responses, also has the ability to modify the electrical characteristics of ganglion cells and thus may modify ganglionic transmission by mechanisms other than antagonism of receptors.