Gating charge interactions with the S1 segment during activation of a Na + channel voltage sensor

Paul G. DeCaen, Vladimir Yarov-Yarovoy, Todd Scheuer, William A. Catterall*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


Voltage-gated Na + channels initiate action potentials during electrical signaling in excitable cells. Opening and closing of the pore of voltage-gated ion channels are mechanically linked to voltagedriven outward movement of the positively charged S4 transmembrane segment in their voltage sensors. Disulfide locking of cysteine residues substituted for the outermost T0 and R1 gating-charge positions and a conserved negative charge (E43) at the extracellular end of the S1 segment of the bacterial Na + channel NaChBac detects molecular interactions that stabilize the resting state of the voltage sensor and define its conformation. Upon depolarization, the more inward gating charges R2 and R3 engage in these molecular interactions as the S4 segment moves outward to its intermediate and activated states. The R4 gating charge does not disulfide-lock with E43, suggesting an outer limit to its transmembrane movement. These molecular interactions reveal how the S4 gating charges are stabilized in the resting state and how their outward movement is catalyzed by interaction with negatively charged residues to effect pore opening and initiate electrical signaling.

Original languageEnglish (US)
Pages (from-to)18825-18830
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number46
StatePublished - Nov 15 2011


  • Sliding helix
  • Voltage-dependent gating

ASJC Scopus subject areas

  • General


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