Access and Binding of Local Anesthetics in the Closed Sodium Channel

Local anesthetics (LAs) are known to bind Na+ channels in the closed, open, and inactivated states and reach their binding sites via extracellular and intracellular access pathways. Despite intensive studies, no atomic-scale theory is available to explain the diverse experimental data on the LA actions. Here we attempt to contribute to this theory by simulating access and binding of LAs in the KcsA-based homology model of the closed Na+ …