FIGURE 11.

Molecular model of the interaction of Cd²⁺ with I_S and I_US. Shown are the S6 segments of two domains. The selectivity filter is indicated by a ring separating the outer vestibule (funnel-like shape) from the inner vestibule (central cavity). The kinetic scheme is analogous to Fig. 8 A. Slow inactivation (I_S) is considered to occur by a collapse of the outer vestibule at the level of the selectivity filter. A further rearrangement, consisting of a widening of the external vestibule and a simultaneous constriction of the inner vestibule, gives rise to I_US. The Cd²⁺-bound states are depicted in the lower row (Cd²⁺ is indicated by the ball). Cd²⁺ binds to all states, but the binding is strongest with the I_S state, producing a constriction of the selectivity filter ring. Hence, Cd²⁺ exposure during the I_US state (wide selectivity filter) promotes the formation of I_S (narrow selectivity filter) thereby speeding recovery from I_US.