Xenbase Image ID: 121032

Figure 7. Comparison of predictions from a “multi-substrate single-file model” and a two-state alternating access model. (A) Multi-substrate single-file transport model for GAT1 (Su et al. 1996). The channel contains three single-file binding sites that can accommodate either GABA or Na+, and the substrates “hop” between them. (B) Simulation of the “trans-effect” of Na+o on the GABAi dependence of outward GAT1 transport current. (C) Simulation of the “cis-effect” of Na+i on the GABAi dependence of outward GAT1 transport current in the presence of Na+o. In both cases, [Na+]i is not limiting and [GABA]o is zero. (D) A two-state alternating-access model for a simulated “XY-cotransporter,” where efflux of X and Y generates outward transport current. The two time-dependent steps (arrow pairs) of the transport cycle are the rearrangement of binding sites in the empty (1) and fully loaded (2) transporters. The equations employed were equivalent to those used for more extensive simulations (Hilgemann and Lu 1999). The intrinsic transition rates for fully loaded and empty binding sites were equal. Double-headed arrows indicate “instantaneous” association/dissociation of the substrates. (E) Comparison of the measured effect of extracellular Na+ on outward GAT1 current with the simulated trans-effect of Xo. Cytoplasmic GABA concentration dependence of the outward GAT1 current with 120 mM cytoplasmic NaCl at 0 mV was measured in the absence (•) or presence (○) of 100 mM Na+o. Solid lines represent simulated Yi dependence of outward transport current when [X]i is not limiting and [Y]o is zero, where the fraction of transporters with Xo bound (fxo) is 0.6 (upper curve) or 1 (lower curve). (F) Comparison of the measured effect of lowering cytoplasmic Cl− on outward GAT1 current with the simulated cis-effect of Xi. Cytoplasmic GABA dependence of the outward GAT1 current with 120 mM extracellular NaCl at 0 mV was measured with 120 mM (•) or 30 mM (○) cytoplasmic Cl−. Solid lines represent the simulated Yi dependence of outward transport current in the presence of Xo (fxo = 0.8) and non-limiting Xi, where the fraction of transporters with Xi bound (fxi) is 1 (upper curve) or 0.4 (lower curve). Image published in: Lu CC and Hilgemann DW (1999) © 1999 The Rockefeller University Press. Creative Commons Attribution-NonCommercial-ShareAlike license Larger Image Printer Friendly View

Return to previous page