Electrophysiological and pharmacological properties of the human brain type IIA Na+ channel expressed in a stable mammalian cell line
Electrophysiological and pharmacological properties of the human brain type IIA Na+ channel expressed in a stable mammalian cell line
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稳定哺乳动物细胞系中表达的人脑 IIA 型 Na 通道的电生理学和药理学特性
DOI：
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
J. Clare
中科院分区：
文献类型：
--
作者：
Xinmin Xie;T. Dale;V. John;H. Cater;T. Peakman;J. Clare
抽象的。克隆人脑电压门控性钠通道IIA型α亚基，并在中国仓鼠卵巢细胞中稳定表达，用全细胞电压钳技术研究其生物物理学和药理学特性。重组细胞的膜去极化引起高达~ 8000 pA的快速瞬时内向电流。通道在-50 mV时激活，在-10 mV至0 mV时达到最大激活。逆转电位为62±2 mV，接近Na+平衡电位。半最大激活和失活电压分别为-24 2 mV和-63 1 mV。河豚毒素可逆地阻断电流，半数最大抑制为13 nM。首次检测了四种常用抗惊厥药物对克隆的人IIA型通道的作用。拉莫三嗪和苯妥英产生浓度和电压依赖性抑制IIA型电流，而丙戊酸钠和加巴喷丁（高达1 mM）没有影响。这些结果表明，重组人IIA型Na+通道进行河豚毒素敏感的Na+电流与重组大鼠脑IIA型和天然大鼠脑Na+通道中观察到的那些类似的属性。这种稳定的细胞系应提供一个有用的工具，更详细的表征人Na+通道的治疗调节剂。
Abstract. The human brain voltage-gated Na+ channel type IIA α subunit was cloned and stably expressed in Chinese hamster ovary cells and its biophysical and pharmacological properties were studied using whole-cell voltage-clamp. Fast, transient inward currents of up to –8000 pA were elicited by membrane depolarization of the recombinant cells. Channels activated at –50 mV and reached maximal activation at –10 mV to 0 mV. The reversal potential was 62±2 mV which is close to the Na+ equilibrium potential. The half-maximal activation and inactivation voltages were –24±2 mV and –63±1 mV, respectively. Currents were reversibly blocked by tetrodotoxin with a half-maximal inhibition of 13 nM. The effects of four commonly used anti-convulsant drugs were examined for the first time on the cloned human type IIA channel. Lamotrigine and phenytoin produced concentration- and voltage-dependent inhibition of the type IIA currents, whereas, sodium valproate and gabapentin (up to 1 mM) had no effect. These results indicate that recombinant human type IIA Na+ channels conduct tetrodotoxin-sensitive Na+ currents with similar properties to those observed in recombinant rat brain type IIA and native rat brain Na+ channels. This stable cell line should provide a useful tool for more detailed characterization of therapeutic modulators of human Na+ channels.
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体细胞系中表达的大鼠脑钠通道的功能特性。
DOI：
10.1126/science.2154850
发表时间：
1990
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Scheuer,T;Auld,VJ;Boyd,S;Offord,J;Dunn,R;Catterall,WA
通讯作者：
Catterall,WA
影响因子：
3.6
作者：
David S. Ragsdale;T. Scheuer;W. Catterall
通讯作者：
David S. Ragsdale;T. Scheuer;W. Catterall
DOI：
10.1073/pnas.77.7.4216
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
URLAUB, G;CHASIN, LA
通讯作者：
CHASIN, LA
人脑电压门控钠通道的一级结构、染色体定位和功能表达。
DOI：
10.1073/pnas.89.17.8220
发表时间：
1992
影响因子：
11.1
作者：
Ahmed,CM;Ware,DH;Lee,SC;Patten,CD;Ferrer-Montiel,AV;Schinder,AF;McPherson,JD;Wagner-McPherson,CB;Wasmuth,JJ;Evans,GA
通讯作者：
Evans,GA
影响因子：
3.6
作者：
Chung-Chin Kuo;Bruce P. Bean
通讯作者：
Chung-Chin Kuo;Bruce P. Bean