Figure 10.

Dependence of the on- and off-rates of QA blockers on their size. The blocker dissociation (A) or association rates (B) are plotted as a function of their ionic radii. The continuous lines are drawn as a visual guide and have no theoretical significance. The decrease of the rates as a function of size is monotonic and there is not a clear cut-off size. Data are mean ± SEM of five to six experiments. (C–E) Cartoon depicting the possible ways in which the QAs may interact with the channel pore. (C) Cartoon of the open-channel pore with a blocker the size of TEA (right) or TPrA (left). (D) A model in which all QAs are only able to access the blocking site when the channel is in the open state, but TEA can reside inside the closed channel (left), whereas larger QAs cannot (right). (E) Alternative model in which the TEA molecule can block the channel in a state-independent manner, whereas the rest of the QAs can only access the blocking site when the channel is open, and hence interact with channel gating. In any way, TEA can reside in its blocking site when the channel is closed, whereas the other QAs do not.