Figure 9. A schematic depicting a preliminary model of sodium channel modulation by local anesthetics. Local anesthetic binding to the open and inactivated state primarily stabilizes the pore segments of domain III and to some extent of domain IV in the open state. Because the movement of pore helices (blue circles) is coupled to the voltage sensor (pink ellipsoids), local anesthetic binding also stabilizes the voltage sensors of domains III and IV in the activated state. The interdomain interaction is mediated by the residues near the inner helix bundle crossing. In this model, as in the potassium channel, these residues interact in the closed state of the channel. This interaction is disrupted if the local anesthetic acts as a wedge and prevents the S6 segments of domains III and IV from fully closing.
Image published in: Muroi Y and Chanda B (2009)
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