Figure 5.

CDI models reveal unique, testable behaviors. (A) (Top) Model 1 represents NMDA receptor association with holoCaM with subsequent Ca²⁺. apoCaM (open white circles) binds Ca²⁺ (solid circles) before binding to the channel. (Middle) Time-dependent behavior of subsystem (dashed box) is given, representing Ca²⁺ binding to CaM using only fast, N-lobe kinetics in response to a train of Ca²⁺ influx from a gating channel. State 2 (CaM bound with Ca²⁺) of the subsystem is pulsatile between P_2,high and P_2,low occupancy probabilities, in tight synchrony with gating. (Bottom) Shown is simplification of a three-state model given rapid equilibration of its subsystem. (B) (Top) Model 2 represents NMDA receptor association with apoCaM with subsequent Ca binding. (Middle) Given is a simplified model 2 assuming N-lobe kinetics. (Bottom) Shown is behavior of condensed state 2, 3 in response to a train of Ca²⁺ in-flux. The pulsatile system oscillates between P_2,3,high and P_2,3,low. P_2,3,low is set by the fraction of channels preassociated with apoCaM at rest, P_2,high. (C) (i) Given here is evaluation of Eq. 7’s corresponding model 1 across all values of P_o. As CaM affinity for the channel is increased, the system exhibits saturation kinetics. As affinity decreases, the system becomes linear. (ii) Deviations of the simplified model in Eq. 7 from numerical integration to the full three-state model did not affect the overall shape or predicted behavior. (iii) Given here is evaluation of Eq. 8’s corresponding model 2 across all values of P_o. As CaM affinity for the channel is increased, the system exhibits a linear trend. As affinity decreases, the system uniquely develops an upward curvature. (iv) Deviations of the simplified model in Eq. 8 from numerical integration in the full three-state model were minimal and did not affect the overall shape or predicted behavior. (D) (Left) Exampled here is single-channel activity elicited by indicated glutamate concentration. (Right) Given here is a calibration curve for glutamate concentration and P_o determined from cell-attached single-channel recordings. To see this figure in color, go online.