Phencyclidine and glycine modulate NMDA-activated high conductance cationic channels by acting at different sites.

Glutamate activates high (40-50 pS) and low (5-15 pS) conductance cationic channels in outside-out patches excised from cultured cortical and cerebellar granule neurons of neonatal rats. In these neurons, the excitatory amino acid N-methyl-D-aspartic acid (NMDA) activates mainly high conductance channels. Phencyclidine (PCP) at 2 microM selectively reduces the number of NMDA-activated channel openings, at 20 microM it reduces the channel open-time. Glycine increases the opening frequency of high conductance NMDA-activated channels. This action is counteracted by PCP. This inhibition by PCP can be eliminated by reversing the polarity of the membrane patch. However, the effect of glycine is voltage independent. These results imply different sites of action for these two modulators.