Goldschen-Ohm Marcel P, Chanda Baron
Department of Neuroscience, University of Wisconsin, Madison, WI, USA.
Handb Exp Pharmacol. 2014;221:183-201. doi: 10.1007/978-3-642-41588-3_9.
Several classes of small molecules and peptides bind at the central pore of voltage-gated sodium channels either from the extracellular or intracellular side of the membrane and block ion conduction through the pore. Biophysical studies that shed light on the chemical nature, accessibility, and kinetics of binding of these naturally occurring and synthetic compounds reveal a wealth of information about how these channels gate. Here, we discuss insights into the structural underpinnings of gating of the channel pore and its coupling to the voltage sensors obtained from pore blockers including site 1 neurotoxins and local anesthetics.
几类小分子和肽从细胞膜的细胞外侧或内侧与电压门控钠通道的中央孔结合，并阻断离子通过该孔的传导。揭示这些天然存在的和合成化合物结合的化学性质、可及性和动力学的生物物理研究，揭示了大量关于这些通道如何门控的信息。在这里，我们讨论从包括1型神经毒素和局部麻醉剂在内的孔道阻滞剂获得的关于通道孔门控的结构基础及其与电压传感器耦合的见解。
