Functional modulation of human brain Naν1.3 sodium channels, expressed in mammalian cells, by auxiliary β1, β2 and β3 subunits
Functional modulation of human brain Naν1.3 sodium channels, expressed in mammalian cells, by auxiliary β1, β2 and β3 subunits
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DOI：
10.1016/s0306-4522(02)00242-7
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发表时间：
2002-01-01
期刊：
影响因子：
3.3
通讯作者：
Ragsdale, DS
中科院分区：
文献类型：
--
作者：
Meadows, LS;Chen, YH;Ragsdale, DS
电压门控钠通道由一个成孔亚基和两个辅助亚基组成。可兴奋细胞表达多个α亚型，指定Na(v)1.1-Na(v)1.9，以及三个β亚基，指定beta1， beta2和beta3。了解不同的a，亚型如何结合各种β亚基决定钠通道行为，对于阐明钠通道功能多样性的分子基础非常重要。本研究采用全细胞电生理记录的方法研究了稳定表达于中国仓鼠卵巢细胞的人Na(v)1.3 α亚型的性质，并探讨了β a1、β a2和β a3亚基对Na(v)1.3 α功能的调节作用。在缺乏β亚基的情况下，人类Na(v)1.3形成的通道迅速失活(tau（失活）接近0。在0毫伏时5毫秒)，并且在190毫秒长的去极化结束时几乎完全消失。使用以天冬氨酸为主要阴离子的细胞内溶液，通道激活的中点类似于-12 mV。使用100毫秒调理脉冲确定的失活中点类似于-47 mV。在-80 mV下，失活通道的重印时间常数近似于6 ms。beta1和beta3的共表达不影响失活时间进程，也不影响活化的电压依赖性，但使失活曲线向负10 mV方向移动，并使复燃速率减慢约3倍。na (v)1.3在受损的伤害性外周传入事件中表达增加。这种通道表达水平的变化与钠电流的快速失活和快速恢复的出现有关，这被认为是神经性疼痛的病理生理学的一部分。本研究结果支持Na(v)1.3可能介导这种快速钠电流的假设。(c) 2002年ibro。Elsevier Science Ltd.出版。版权所有。
Voltage-gated sodium channels consist of a pore-forming a subunit and two auxiliary beta subunits. Excitable cells express multiple alpha subtypes, designated Na(v)1.1-Na(v)1.9, and three beta subunits, designated beta1, beta2 and beta3. Understanding how the different a, subtypes, in combination with the various beta subunits, determine sodium channel behavior is important for elucidating the molecular basis of sodium channel functional diversity. In this study, we used whole-cell electrophysiological recording to examine the properties of the human Na(v)1.3 alpha subtype, stably expressed in Chinese hamster ovary cells, and to investigate modulation of Na(v)1.3 function by beta1, beta2 and beta3 subunits. In the absence of beta subunits, human Na(v)1.3 formed channels that inactivated rapidly (tau(inactivation) approximate to 0. 5 ms at 0 mV) and almost completely by the end of 190-ms-long depolarizations. Using an intracellular solution with aspartate as the main anion, the midpoint for channel activation was similar to -12 mV. The midpoint for inactivation, determined using 100-ms conditioning pulses, was similar to -47 mV. The time constant for reprinting of inactivated channels at -80 mV was similar to6 ms. Coexpression of beta1 or beta3 did not affect inactivation time course or the voltage dependence of activation, but shifted the inactivation curve similar to10 mV negative, and slowed the repriming rate ca. three-fold. 2 did not affect channel properties, either by itself or in combination with betaI or beta3.Na(v)1.3 expression is increased in damaged nociceptive peripheral afferents. This change in channel expression levels is correlated with the emergence of a rapidly inactivating and rapidly repriming sodium current, which has been proposed to contribute to the pathophysiology of neuropathic pain. The results of this study support the hypothesis that Na(v)1.3 may mediate this fast sodium current. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.