Figure 7.

Possible models for chloride movement during depolarization-activated fast gating. Evidence from previously published papers and our kinetic and homology model analysis was used to narrow down the possible models for chloride movement during depolarization-activated fast-gate opening to those shown (see text). The channel begins in the closed state C, binds chloride to reach the closed state C·Cl, and then goes through another depolarization-activated transition to reach the open state O. This is depicted at the top of both A and B. K _c is the apparent equilibrium constant for chloride dissociation, and α₂ ^* is the rate constant for the second step, C·Cl→O. In A, depicted below each of these states (C, C·Cl, and O) are their possible chloride occupancy states, with empty circles depicting vacant chloride binding sites, and filled circles depicting filled chloride binding sites. Lines between these chloride-occupancy states indicate transitions corresponding to either C→C·Cl or C·Cl→O. Dashed lines indicate C·Cl→O transitions that involve chloride binding to the pore. Evidence from our analysis of gating kinetics and the ClC-0 homology models further narrowed the possibilities to those shown in B. In Model 1, the dashed line outlines the microstates that are all part of C·Cl. K ₁, K ₂, and K ₃ are microscopic equilibrium constants, and k ₄ is a microscopic rate constant. In Model 2, the second step has to involve some conformational change that opens the channel but does not change chloride occupancy.