BOTH OPEN AND CLOSED NMDA RECEPTOR CHANNELS DESENSITIZE

Desensitization of NMDA receptors was studied at the single-channel le vel using outside-out patches taken from rat hippocampus CA neurons ma intained short term in culture. The amount of desensitization that acc umulated as a function of time during the application of NMDA (2.5 mu M) was measured by the response to the rapid application of NMDA at a high concentration (100 mu M) Records were sorted into two classes: th ose in which no openings were detected during the application of 2.5 m u M NMDA, and those in which some channel openings occurred. Analysis of these data reveals that some desensitization accumulated when no ch annels opened, but that more desensitization developed when channels o pened. The observations indicate that channels can pass from the close d state to the desensitized state, but that desensitization occurs mor e rapidly from the open state.