Voltage sensors in domains III and IV, but not I and II, are immobilized by Na+ channel fast inactivation

Cha Albert, Peter C. Ruben, Alfred L. George, Esther Fujimoto, Francisco Bezanilla*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

204 Scopus citations

Abstract

Using site-directed fluorescent labeling, we examined conformational changes in the S4 segment of each domain of the human skeletal muscle sodium channel (hSkM1). The fluorescence signals from S4 segments in domains I and II follow activation and are unaffected as fast inactivation settles. In contrast, the fluorescence signals from S4 segments in domains III and IV show kinetic components during activation and deactivation that correlate with fast inactivation and charge immobilization. These results indicate that in hSkM1, the S4 segments in domains III and IV are responsible for voltage- sensitive conformational changes linked to fast inactivation and are immobilized by fast inactivation, while the S4 segments in domains I and II are unaffected by fast inactivation.

Original languageEnglish (US)
Pages (from-to)73-87
Number of pages15
JournalNeuron
Volume22
Issue number1
DOIs
StatePublished - Jan 1999

ASJC Scopus subject areas

  • Neuroscience(all)

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