Members of the voltage-gated ion channel superfamily (VGIC) respond to voltage changes by opening and closing a central pore. The mechanics and the molecular details of coupling between voltage-sensing motions and pore gates remain poorly understood. Using two complementary methods, we have identified a common set of residues in the S4-S5 linker and S6 of domain III that are primarily involved in electromechanical coupling between voltage-sensor of domain III and the pore gates. This is first study to examine electromechanical coupling in ion channels that lack the symmetry of the voltage-gated potassium channels and shows that the site of coupling may be conserved in this superfamily.

  1. Muroi Y, Chanda B. Local anesthetics disrupt energetic coupling between the voltage-sensing segments of a sodium channel. J Gen Physiol. 2009 Jan;133(1):1-15. PubMed PMID: 19088384; PubMed Central PMCID: PMC2606943.
  2. Muroi Y, Arcisio-Miranda M, Chowdhury S, Chanda B. Molecular determinants of coupling between the domain III voltage sensor and pore of a sodium channel. Nat Struct Mol Biol. 2010 Feb;17(2):230-7. PubMed PMID: 20118934; PubMed Central PMCID: PMC2879147.
  3. Arcisio-Miranda M, Muroi Y, Chowdhury S, Chanda B. Molecular mechanism of allosteric modification of voltage-dependent sodium channels by local anesthetics. J Gen Physiol. 2010 Nov;136(5):541-54. PubMed PMID: 20937693; PubMed Central PMCID: PMC2964522.
  4. Chowdhury S, Chanda B. Perspectives on: conformational coupling in ion channels: thermodynamics of electromechanical coupling in voltage-gated ion channels. J Gen Physiol. 2012 Dec;140(6):613-23. PubMed PMID: 23183697; PubMed Central PMCID: PMC3514737.