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.
Ashford
M L
ML
Zoology Department, Nottingham University, University Park, UK.
Boden
P
P
Ramsey
R L
RL
Usherwood
P N
PN
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006110:Grasshoppers / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D007649:Ketamine / Q000494:pharmacology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D010069:Oxadiazoles / Q000494:pharmacology*; D016318:Quisqualic Acid; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*
D005971:Glutamates; D007473:Ion Channels; D010069:Oxadiazoles; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D003208:Concanavalin A; D018698:Glutamic Acid; D007649:Ketamine; D016318:Quisqualic Acid