Modified behavioral characteristics following ablation of the voltage-dependent calcium channel β3 subunit
Modified behavioral characteristics following ablation of the voltage-dependent calcium channel β3 subunit
复制标题
DOI：
10.1016/j.brainres.2007.05.041
复制
发表时间：
2007-07-30
期刊：
影响因子：
2.9
通讯作者：
Iijima, Toshihiko
中科院分区：
文献类型：
--
作者：
Murakami, Manabu;Nakagawasai, Osamu;Iijima, Toshihiko
电压依赖性钙通道对于各种可兴奋膜中的钙内流和随后的细胞内钙信号是重要的。这些通道的β亚基通过高压激活的钙通道的成孔α 1亚基来改变钙电流。在本研究中，使用3个亚基缺失小鼠来研究电压依赖性钙通道的β 3亚基的重要性，其与CaV2.2（α 1B）亚基偶联形成脑中神经元N型钙通道的主要组分。蛋白质印迹分析显示，β 3亚基缺失小鼠的N型钙通道显著减少，而其他高电压激活的钙通道α 1亚基的蛋白质水平不变。用抗CaV2.2抗体进行的免疫沉淀分析表明，在β 3亚基缺失小鼠中发生了N型通道组装的重组.该亚基的消融导致了伤害感受的改变、焦虑的减少和攻击性的增加。β 3亚基缺失的小鼠也表现出学习能力受损。这些结果表明电压依赖性钙通道的重要性和β 3亚基在记忆形成、伤害性感觉转导和各种神经信号转导途径中的关键作用。(C)2007 Elsevier B.V.保留所有权利。
Voltage-dependent calcium channels are important for calcium influx and the ensuing intracellular calcium signal in various excitable membranes. The beta subunits of these channels modify calcium currents through pore-forming al subunits of the high-voltage-activated calcium channels. In the present study, 3 subunit-null mice were used to investigate the importance of the beta 3 subunit of the voltage-dependent calcium channel, which couples with the CaV2.2 (alpha 1B) subunit to form the major component of neuronal N-type calcium channels in the brain. Western blot analysis revealed a significant decrease in N-type calcium channels in beta 3 subunit-null mice, while protein levels of other high-voltage-activated calcium channel alpha 1 subunits were unchanged. Immunoprecipitation analysis with an anti-CaV2.2 antibody showed that reshuffling of the assembly of N-type channels had occurred in the beta 3 subunit-null mice. Ablation of this subunit resulted in modified nociception, decreased anxiety, and increased aggression. The beta 3 subunit-null mice also showed impaired learning ability. These results suggest the importance of voltage-dependent calcium channels and the key role of the beta 3 subunit in memory formation, nociceptive sensory transduction, and various neurological signal transduction pathways. (C) 2007 Elsevier B.V. All rights reserved.