标题：Reduced sodium channel density, altered voltage dependence of inactivation, and increased susceptibility to seizures in mice lacking sodium channel β2-subunits
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：26
页码：17072-17077
DOI：10.1073/pnas.212638099
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Sodium channel {beta}-subunits modulate channel gating, assembly, and cell surface expression in heterologous cell systems. We generated {beta}2-/- mice to investigate the role of {beta}2 in control of sodium channel density, localization, and function in neurons in vivo. Measurements of [3H]saxitoxin (STX) binding showed a significant reduction in the level of plasma membrane sodium channels in {beta}2-/- neurons. The loss of {beta}2 resulted in negative shifts in the voltage dependence of inactivation as well as significant decreases in sodium current density in acutely dissociated hippocampal neurons. The integral of the compound action potential in optic nerve was significantly reduced, and the threshold for action potential generation was increased, indicating a reduction in the level of functional plasma membrane sodium channels. In contrast, the conduction velocity, the number and size of axons in the optic nerve, and the specific localization of Nav1.6 channels in the nodes of Ranvier were unchanged. {beta}2-/- mice displayed increased susceptibility to seizures, as indicated by reduced latency and threshold for pilocarpine-induced seizures, but seemed normal in other neurological tests. Our observations show that {beta}2-subunits play an important role in the regulation of sodium channel density and function in neurons in vivo and are required for normal action potential generation and control of excitability.
