Enhancement of Desensitization of Quisqualate-Type Glutamate Receptor by the Dissociative Anaesthetic Ketamine

Application of ketamine (10(-4)-10(-3)mol l-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 (5 x 10(-5)-10(-3) mol l-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) mol l-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)-5 x 10(-4) mol l-1) in a dose-dependent manner but without a concomitant reduction in EPSC rise time. The decay phase of the EPSC was usually biphasic in the presence of ketamine (greater than 5 x 10(-5) mol l-1) but did not exhibit any voltage dependence. It is concluded that ketamine enhances desensitization and blocks the channel, particularly the closed form.