Figure 9.

Models of Tl⁺ interaction with the thiolate groups of C169 and open↔ close transitions of channels in the presence external Tl⁺. (A) The schematics represent cross sections of the pore at the position of C169. Under our recording conditions, the external and internal permeant ion species are Tl⁺ and K⁺, respectively. When the channel is closed, due to conformational changes in the selectivity filter, the cavity is equilibrated with the internal solution and is presumably occupied by K⁺, which interacts weakly with the thiolate groups (I). As Tl⁺ permeates the cavity immediately following channel opening, it induces a reorientation of the thiolate groups and seeks to form an optimal coordination (II). This process triggers a slow conformational change of the pore, such as a constriction (but the exact nature of the conformational change is unclear). Two models are proposed for the subsequent interaction between Tl⁺ and the thiolate groups. In one case (III), the permeating Tl⁺ is optimally coordinated by all four thiolate groups, but its residence time is <50 ns. In another case (IV), a Tl⁺ is optimally and tightly coordinated by three thiolate groups, and the cavity is sufficiently wide to permit Tl⁺ ions to flow by the bound Tl⁺. (B) A qualitative model of transitions among the proposed closed and open states in the presence of external Tl⁺ (discussion). (C) An idealized single-channel Tl⁺ current trace. The two predominant types of channel openings, C_f to O_f and C_s to O_s, are preceded by two and one closed states, respectively.