Figure 2. Markov model of NMDAR activation.

A, reaction scheme shows two molecules of glutamate (A) binding to the NMDA receptor (R), opening of the channel (O), and transition to fast and slow desensitization states (D_f and D_s). Mg²⁺ binds to all five states, although binding is much more rapid to the open state (thick lines) than to the other states (dashed lines). B, recorded and simulated NMDAR current during 4.6 s applications of 1 mm glutamate in the presence of 1 mm Mg²⁺ at holding potentials of −60 and +40 mV (black), and during a step from −60 to +40 mV starting 10 ms (see inset with expanded time scale) or 3.5 s after the glutamate application (grey). Fitted transients (smooth curves) generated by the model shown in A are superimposed on the data.