Cha A, Ruben P C, George A L, Fujimoto E, Bezanilla F
Department of Physiology, University of California School of Medicine, Los Angeles 90095, USA.
Neuron. 1999 Jan;22(1):73-87. doi: 10.1016/s0896-6273(00)80680-7.
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.
利用定点荧光标记技术,我们检测了人类骨骼肌钠通道(hSkM1)每个结构域的S4片段的构象变化。结构域I和II中S4片段的荧光信号随激活而变化,在快速失活稳定时不受影响。相比之下,结构域III和IV中S4片段的荧光信号在激活和失活过程中显示出与快速失活和电荷固定相关的动力学成分。这些结果表明,在hSkM1中,结构域III和IV中的S4片段负责与快速失活相关的电压敏感构象变化,并因快速失活而固定,而结构域I和II中的S4片段不受快速失活的影响。