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. Material and 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. Conclusion-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.