Kinetics of NMDA Channel Opening

Abstract

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