Studies on the mechanism of action of acetylcholine antagonists on rat parasympathetic ganglion cells

The Journal of Physiology
P AscherH P Rang


The mode of action of ACh antagonists on the parasympathetic neurones of the submandibular ganglion of the rat was studied by means of a two-micro-electrode voltage-clamp technique. The currents produced by various agonists (carbachol, ACh, suberylcholine) were studied in steady state and after voltage steps, before and after perfusion of various antagonists. 2. For three antagonists (tubocurarine, hexamethonium, decamethonium) the blocking action increases with hyperpolarization. For three other antagonists (surugatoxin, trimetaphan, mecamylamine) the effects observed at low concentrations appear to be independent of membrane potential, although in some cases voltage dependence of the block was observed for mecamylamine. 3. The blocks the 'open' channel-reception complex. The block produced by tubocurarine, hexamethonium and decamethonium increases with the agonist concentration, an observation which supports a 'sequential' scheme in which the antagonist blocks the 'open' channel-receptor complex. The block produced by trimetaphan and mecamylamine decreases slightly with increased agonist concentration, which in turn suggests that these two compounds are competitive antagonists, preventing binding of the agonists to the closed...Continue Reading


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