Intracellular recording techniques were used to examine the action of an irreversible acetylcholine esterase (AChE) inhibitor, soman, on the hyperpolarizations mediated through muscarinic cholinoceptors in cat bladder parasympathetic neurones. 2. Soman (0.1-10 microM) depressed the amplitude and prolonged the duration of the muscarinic slow inhibitory postsynaptic potential (s-i.p.s.p.) elicited by a preganglionic tetanus (40 Hz for 1 s) in the presence of mecamylamine (20 microM), phentolamine (1 microM) and caffeine (1 mM), in a dose-dependent manner. The effect of soman on the amplitude of the s-i.p.s.p. was partially reversible, while the effect on the duration was irreversible. 3. Soman hyperpolarized the membrane and decreased input resistance, but this effect could not account for soman-induced inhibition of the s-i.p.s.p. 4. Soman depressed the amplitude and prolonged the duration of a muscarinic hyperpolarization induced by pressure application of acetylcholine (ACh) in the presence of mecamylamine, phentolamine and caffeine. The time course of this effect paralleled that on the synaptically-evoked muscarinic s-i.p.s.p. 5. A reversible AChE inhibitor, pyridostigmine (10-100 microM), also depressed the amplitude and prolonged the duration of a muscarinic hyperpolarization induced by either preganglionic stimulation or ACh pressure application. These actions were reversible, and not accompanied by a significant change in membrane potential or input resistance. 6. The inhibitory action of soman (1 microM) on the muscarinic hyperpolarization was prevented by pyridostigmine (10 microM), but not by atropine (1 microM). 7. These results demonstrate that soman prolongs not only the muscarinic hyperpolarization, but also inhibits its amplitude through a postsynaptic action, probably through AChE inhibition, in cat bladder parasympathetic neurones.
