Blockade of cholinergic channels by chlorisondamine on a crustacean muscle.

Abstract

SUMMARY1. Details of the blocking action of chlorisondamine, a ganglionic nicotinic blocker, on the excitatory cholinergic currents ofthe spiny lobster gastric mill 1 (g.m. 1) muscle are described.2. The steady-state block of cholinergic ionophoretic currents produced by chlorisondamine is strongly voltage-dependent.3. 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.4. 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.5. 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).6. 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 ( -35 mV/e-fold change). 7. Reduction in the amplitude of e.j.c.s occurred at concentrations of chlorisondamine that produced no detectable effect on e.j.c. decay.8. Alterations in e.j.c. amplitude showed time-and use-dependent aspects similar to those observed for ionophoretic currents.9. 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.

Desensitization of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors Facilitates Use-Dependent Inhibition by Pentobarbital

“…A common property of open channel blockers is their ability to remain bound or "trapped" to a closed state of the receptor after the unbinding of agonist (Lingle, 1983;Chen and Lipton, 1997). A trapping protocol ( Fig.…”

Amantadine Inhibits NMDA Receptors by Accelerating Channel Closure during Channel Block

“…3A) is derived from previous work on channel block of NMDA receptors (Benveniste and Mayer, 1995;Blanpied et al, 1997;Chen and Lipton, 1997;Dilmore and Johnson, 1998;Sobolevsky and Yelshansky, 2000) and nicotinic ACh receptors (Lingle, 1983;Ogden and Colquhoun, 1985). The upper five states of model 1 describe the behavior of NMDA receptors in the absence of blocker, whereas the lower five states describe the ability of amantadine to be trapped in closed channels.…”

Anomalous voltage dependence of channel blockade at a crustacean glutamate‐mediated synapse.

“…closinig. There is now substanitial preceedence for cases in which ions or other agents may become trapped within channiels upon (channtiel closure (Armstrong, 1971;Jingle, 1983a,b;Gurney & Rang, 1984;Miller, 1987) and, in fact, chlorisondamine appears to become trapped in acetyicholine-activated channels (Lingle. 1983a(;Neelv & Lingle, 1986).…”