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 language | English (US) |
|---|---|
| Pages (from-to) | 73-87 |
| Number of pages | 15 |
| Journal | Neuron |
| Volume | 22 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1999 |
Funding
This work was supported by National Institutes of Health grant GM-30376 and the Hagiwara Chair funds (F. B.), National Institutes of Health grant NS-29204 and the Muscular Dystrophy Association (P. R. and E. F.), and National Institutes of Health grant NS-32387 (A. G.). A. C. is supported by the UCLA Medical Scientist Training Program (GM-08042) and a National Research Service Award from the National Institute of Mental Health (MH-12087). We would like to thank Dr. Ramon Latorre for comments on the manuscript.
ASJC Scopus subject areas
- General Neuroscience