Voltage-Dependent Block of Locust Muscle Glutamate Channels by Chlorisondamine

Chlorisondamine reversibly reduced the amplitude of the neurally evoked twitch of locust retractor unguis muscle in a dose-dependent manner and also blocked agonist-induced contractions. Depolarizations elicited by ionophoresis of 1-glutamate were also reduced in amplitude by chlorisondamine, but there was no effect of this drug on desensitization. Neurally evoked synaptic currents were reduced in amplitude, their rise time was decreased and their decay phase made biphasic (or more complex) by chlorisondamine (>10−5 mol 1−1). These effects of chlorisondamine were voltage-dependent, such that at very hyperpolarized potentials (−120 mV and −140 mV) there was an apparent reduction in the degree of block. Single-channel studies indicate that chlorisondamine acts to block the channel both in the open and the closed form and that these actions are dependent on concentration and voltage. The actions of chlorisondamine are discussed in relation to the basic kinetic models of channel block.