Voltage-gating in Eukaryotic Sodium Channels

According to the coupled inactivation model, all four voltage-sensors activate and contribute to the opening of the sodium channel and binding of the inactivation particle to open channels result in inactivation. By combining spectroscopic and electrophysiological methods, we found that the activation of domain IV precedes inactivation and its movement is both rate limiting and sufficient. These studies reveal the nature of the conformational change in the sodium channel and highlight a distinct mechanism of inactivation that is not observed in canonical voltage-gated potassium channels (also see Ahern(2013) JGP; 97-100). I initiated this work as a postdoctoral researcher but bulk of this work was carried out in my group at UW-Madison.

  1. Ahern CA, Payandeh J, Bosmans F, Chanda B. The hitchhiker’s guide to the voltage-gated sodium channel galaxy. J Gen Physiol. 2016 Jan;147(1):1-24. PubMed PMID: 26712848; PubMed Central PMCID: PMC4692491.
  2. Capes DL, Goldschen-Ohm MP, Arcisio-Miranda M, Bezanilla F, Chanda B. Domain IV voltage-sensor movement is both sufficient and rate limiting for fast inactivation in sodium channels. J Gen Physiol. 2013 Aug;142(2):101-12. PubMed PMID: 23858005; PubMed Central PMCID: PMC3727307.
  3. Goldschen-Ohm MP, Capes DL, Oelstrom KM, Chanda B. Multiple pore conformations driven by asynchronous movements of voltage sensors in a eukaryotic sodium channel. Nat Commun. 2013;4:1350. PubMed PMID: 23322038; PubMed Central PMCID: PMC3562458.
  4. Chanda B, Bezanilla F. Tracking voltage-dependent conformational changes in skeletal muscle sodium channel during activation. J Gen Physiol. 2002 Nov;120(5):629-45. PubMed PMID: 12407076; PubMed Central PMCID: PMC2229551.

Check out commentary by Chris Ahern (JGP(2013); 97-100)