Rapid decay of averaged single-channel NMDA receptor activations recorded at low agonist concentration

T he N M D A class of g lu tam ate receptors have the unique property of binding some agonists, including glutam ate, for a very long period of time. O ne manifestation of this is tha t brief (1 ms) application of g lu tam ate (1 him) produces a slowly decaying current, the m ajor com ponent of which has a time constant of approxim ately 200 ms. Application of g lu tam ate a t low concentrations allows identification of groups (‘superclusters’) of openings in the da ta record tha t probably correspond to a single period during which one or more molecules of g lu tam ate are bound to the receptor, i.e. a single activation of the channel. The length of such superclusters is long on average (74 m s); the longest com ponent of the distribution has a duration of approxim ately 300 ms, and comprises about 25 % of the area. However, aligning m any superclusters to obtain an average current reveals that the decay is m ainly fast; the m ajor com ponent has a time constant of around only 5 ms. I t is shown tha t incorporation of a distribution of first latencies (from the time of the ju m p to the first opening) can explain at least p art of this discrepancy.