Blockade of cholinergic channels by chlorisondamine on a crustacean muscle.
Details of the blocking action of chlorisondamine, a ganglionic nicotinic blocker, on the excitatory cholinergic currents of the spiny lobster gastric mill 1 (g.m.1) muscle are described. The steady-state block of cholinergic ionophoretic currents produced by chlorisondamine is strongly voltage-dependent. During a hyperpolarizing voltage step, a sequence of ionophoretic agonist pulses in the presence of chlorisondamine shows a large interpulse interaction manifested as a gradual diminution in response amplitude. The extent of diminution is dependent on the number of the pulse in a series and not on the duration of the interval between pulses. The slowly developing blockade is entirely dependent on agonist application. If agonist application is suspended for various time intervals following the development of a given blocked level in chlorisondamine, no recovery from the block is observed whether the rest interval is at the step potential or at more depolarized potentials. Recovery from a given blocked level can be observed if, during a depolarizing voltage step (to -60 mV) away from the potential at which the block was established (-140 mV), agonist is applied before return to the initial potential (-140 mV). Chlorisondamine produces a dose-dependent reduction in excitatory junctional current (e.j.c.) decay rate that is linear with chlorisondamine concentration and markedly dependent on voltage (approximately equal to 35 mV/e-fold change). Reduction in the amplitude of e.j.c.s occurred at concentrations of chlorisondamine that produced no detectable effect on e.j.c. decay. Alterations in e.j.c. amplitude showed time- and use-dependent aspects similar to those observed for ionophoretic currents. These results are discussed primarily in terms of a sequential model in which, following the binding of chlorisondamine to the opened ion channel, the channel can undergo a transition to a stable-blocked state that requires reactivation by agonist to become unblocked. This stable-blocked state is considered a closed-blocked channel.
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D002714:Chlorisondamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009132:Muscles / Q000187:drug effects; D008121:Nephropidae; D011950:Receptors, Cholinergic / Q000187:drug effects*; D013570:Synaptic Membranes / Q000187:drug effects; D013997:Time Factors
D007473:Ion Channels; D011950:Receptors, Cholinergic; D002714:Chlorisondamine; D000109:Acetylcholine