Patton D E, West J W, Catterall W A, Goldin A L
Department of Microbiology and Molecular Genetics, University of California, Irvine 92717.
Neuron. 1993 Nov;11(5):967-74. doi: 10.1016/0896-6273(93)90125-b.
The short cytoplasmic peptide segment connecting domains III and IV of voltage-gated sodium channels (III-IV linker) is essential for fast inactivation. To test the functional similarity between the III-IV linker and the potassium channel inactivation particle, we attached the III-IV linker to the amino terminus of a noninactivating potassium channel. This chimeric channel inactivated rapidly and displayed biophysical properties similar to Shaker A-type potassium channels. Recovery from inactivation in the chimeric channels was accelerated by high external potassium, consistent with the idea that potassium ions passing through the channel displaced the III-IV linker inactivation particle. A mutation that completely abolishes fast inactivation in rat brain sodium channels also completely abolished inactivation in the chimera. These results demonstrate that the sodium channel III-IV linker can function as a fast inactivation gate and suggest a functional relationship between the fast inactivation processes of sodium and potassium channels.
连接电压门控钠通道结构域III和IV的短细胞质肽段（III-IV连接子）对快速失活至关重要。为了测试III-IV连接子与钾通道失活颗粒之间的功能相似性，我们将III-IV连接子连接到一个非失活钾通道的氨基末端。这种嵌合通道迅速失活，并表现出与Shaker A型钾通道相似的生物物理特性。高细胞外钾加速了嵌合通道的失活恢复，这与钾离子通过通道取代III-IV连接子失活颗粒的观点一致。一个完全消除大鼠脑钠通道快速失活的突变也完全消除了嵌合体中的失活。这些结果表明，钠通道III-IV连接子可作为快速失活门，并提示钠通道和钾通道快速失活过程之间存在功能关系。
