Fig. 3.

Characteristics of current responses to applied agonists depend on the time exposure of the agonist and on the temporal profile of the agonist transient. (a) the frame of the Jones and Westbrook’s model of GABA_A receptor gating (Jones and Westbrook 1995). Rate constants for simulations are from Mozrzymas and others (2003b): kon = 6 ms^-1mM^-1; k_off = 1 ms^-1; β₁ = 0.15 ms^-1, α₁ = 1.5 ms^-1, d₁ = 0.045 ms^-1, r₁ = 0.014 ms^-1; β₂ = 3 ms^-1, α₂ = 0.4 ms^-1, d₂ = 12 ms^-1, r₂ = 0.07 ms^-1. (b) dose-response relationship for peak currents (simulated as the sum of open states occupancies) evoked by GABA applications sufficiently long to reach maximum value at given agonist concentration. At 1 mM current amplitude reaches 93 % of maximum response. (c) simulated current responses to rectangular GABA pulse (1 mM) of various duration from 0.05 to 1 ms. Note that for 0.1 ms pulse duration, current response reaches less than one third of response elicited by 1 ms application. In (d) the peak values of simulated currents presented in (c) are presented versus time duration of GABA pulse (1 mM). (e) comparison of simulated currents elicited by a rectangular GABA pulse (1 mM, 0.1 ms, thin line) to the current evoked by exponentially decaying GABA application (A×exp(-t/τ) where A = 1 mM, τ = 0.1 ms, thick line). Note that averaged exposure to the agonist is the same in both cases but the time course of currents show marked differences.