Figure 1.

When can an extracellular blocker enter the selectivity filter? (A) An intracellular gate predicts equal access to open and closed channels. The solid circles represent Y³⁺ ions. Four negative charges are shown in the Ca²⁺ channel selectivity filter, located near the extracellular side of the ion-conducting pore (Kuo and Hess, 1993; Yang et al., 1993). (B) Ca²⁺ ions in the pore may slow entry of Y³⁺ into closed channels. Open circles are Ca²⁺ ions, at the selectivity filter, and by analogy to K⁺ channels (Doyle et al., 1998) in the inner vestibule. (C) A conceptual model for Y³⁺ block of T-channels. Full models for gating of α1G include multiple closed states, and closed-inactivated states (Serrano et al., 1999; Burgess et al., 2002). Solid arrows indicate transitions that are well established for block of calcium channels by di- and trivalent cations. This paper also considers the possible C ↔ CB step, but not OB ↔ IB or I ↔ IB.