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ENHANCEMENT OF DESENSITIZATION OF QUISQUALATE- TYPE GLUTAMATE RECEPTOR BY THE DISSOCIATIVE ANAESTHETIC KETAMINE

By M. L. J. Ashford, P. Bodent, R. L. Ramsey and P. N. R. Usherwood

Abstract

Application of ketamine (10-4-10 ~ 3 moll ~ 1) to locust retractor unguis muscle produced a reversible, dose-dependent reduction in neurally evoked twitches, and blocked agonist-induced contractions. With increasing ketamine concentration (5xlO " 5-10 ~ 3 moll ~ 1), the amplitude of glutamate potentials was reduced and dose-response curves for ionophoresis of L-glutamate were shifted to the right, particularly after concanavalin A treatment. Ketamine (10 " 4 moir 1) enhanced the rate of desensitization to consecutive pulses of L-glutamate and this action was eliminated by concanavalin A. The amplitude of the excitatory postsynaptic current (EPSC) was reduced by ketamine (10 ~ 5-5xl0 " 4 molP 1) in a dosedependent manner but without a concomitant reduction in EPSC rise time. The decay phase of the EPSC was usually biphasic in the presence of ketamine (>5xlO ~ 5 moll ~ 1) but did not exhibit any voltage dependence. It is concluded that ketamine enhances desensitization and blocks the channel, particularly the closed form

Year: 1988
OAI identifier: oai:CiteSeerX.psu:10.1.1.320.9911
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