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The voltage dependence, concentration dependence, and agonist dependence of blocking and unblocking produced by anticholinergic agents on the ionophoretically activated cholinergic currents of the lobster gastric mill 1 (g.m.1) muscle were examined. Although the ionophoretic technique provides only qualitative information as to blocking mechanisms it is useful in revealing slow components of the blocking action of some drugs. At least two qualitatively different types of voltage-dependent block of the crustacean cholinergic currents were observed. For pempidine, mecamylamine and decamethonium (also chlorisondamine: Lingle, 1983), a slowly developing voltage-dependent block was produced that led to the formation of a stable-blocked state. Recovery from this stable-blocked state is largely dependent on subsequent application of agonist. In contrast, recovery from the voltage-dependent block produced by QX-222, atropine, procaine and curare either proceeds independently of agonist application or occurs too rapidly to be observed by the present methods. Blockade by hexamethonium reveals anomalous voltage dependence, being enhanced over some voltages and relieved with additional hyperpolarization. Blockade by trimetaphan is largely independent of membrane potential except at higher concentrations.

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