TY - JOUR
T1 - Voltage sensors in domains III and IV, but not I and II, are immobilized by Na+ channel fast inactivation
AU - Albert, Cha
AU - Ruben, Peter C.
AU - George, Alfred L.
AU - Fujimoto, Esther
AU - Bezanilla, Francisco
N1 - Funding Information:
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.
PY - 1999/1
Y1 - 1999/1
N2 - 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.
AB - 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.
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U2 - 10.1016/S0896-6273(00)80680-7
DO - 10.1016/S0896-6273(00)80680-7
M3 - Article
C2 - 10027291
AN - SCOPUS:0032963770
VL - 22
SP - 73
EP - 87
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 1
ER -