Ketamine blocks non-N-methyl-D-aspartate receptor channels attenuating glutamatergic transmission in the auditory cortex.
OBJECTIVE
To investigate the influence of ketamine on non-N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission in the auditory cortex.


METHODS
Using whole-cell patch-clamp techniques on pyramidal neurons, we studied the effects of ketamine on excitatory post-synaptic potentials (EPSPs) evoked by electrical stimulation of internal capsule fibers in slices of gerbil auditory cortex.


RESULTS
After blockade of the slow, NMDA receptor-mediated EPSP component with DL-2-amino-5-phosphonovaleric acid, application of ketamine in a concentration-dependent manner led to a reduction in the amplitude of fast, 6-cyano-7-nitroquinoxalinedione (CNQX)-sensitive EPSPs, accompanied by an increased membrane resistance. Blockade of non-NMDA glutamate receptors with CNQX prevented both effects.


CONCLUSIONS
Ketamine reduces membrane conductance and glutamatergic excitation, in part by blocking alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor channels that may be constitutively active at a low level in slice preparations of auditory cortex.
Leong
Darrell
D
Department of Surgery (Otolaryngology), University of British Columbia, Vancouver, BC, Canada.
Puil
Ernest
E
Schwarz
Dietrich
D
D000200:Action Potentials / Q000187:drug effects; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D001303:Auditory Cortex / Q000378:metabolism / Q000502:physiology*; D003864:Depression, Chemical; D004558:Electric Stimulation; D005849:Gerbillinae; D007649:Ketamine / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D000778:Anesthetics, Dissociative; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine