KINETICS OF NMDA CHANNEL OPENING

The period required for NMDA channels to open for the first lime after agonist binding (the first latency) was estimated in outside-out patc h recordings from rat hippocampal neurons using fast-application techn iques and the open channel blocker MK-801. In the presence of MK-801, brief applications of L-glutamate or the low-affinity agonist L-cystea te resulted in a similar amount of block despite the much shorter peri od of channel activation by L-cysteate, A brief coapplication of L-glu tamate and MK-801 resulted in a block similar to that found with an ap plication of L-glutamate in a background of MK-801. These results, alo ng with our findings that MK-801 does not block desensitized receptors , indicate that NMDA channels have a mean first latency of similar to 10 msec, consistent with a peak open probability near 0.3. If NMDA cha nnels at synapses behave similarly, relatively few channels would be r equired to produce the postsynaptic calcium transient associated with synaptic plasticity and developmental regulation.