Triggers of paroxysmal dyskinesia in the calcium channel mouse mutant tottering
Triggers of paroxysmal dyskinesia in the calcium channel mouse mutant tottering
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DOI：
10.1016/s0091-3057(02)00854-7
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发表时间：
2002-10-01
影响因子：
3.6
通讯作者：
Hess, EJ
中科院分区：
文献类型：
--
作者：
Fureman, BE;Jinnah, HA;Hess, EJ
离子通道的突变或通道病通常会导致神经系统疾病，其中正常行为会因疼痛、虚弱或运动控制异常等衰弱症状的发作而中断。发作通常由类似的刺激引起，包括压力、咖啡因、乙醇、运动或疲劳。蹒跚的小鼠遗传了P/Q型钙通道的突变，并可靠地表现出异常运动或运动障碍的发作。为了确定这种小鼠突变体是否是研究发作性神经系统疾病的合适模型，将蹒跚的小鼠暴露于不同的环境条件或已知会促使人类发作的药物。压力、咖啡因和酒精都能可靠地诱发蹒跚小鼠的发作。由于钙内流先前已涉及应激诱导的蹒跚小鼠攻击，L-型钙通道拮抗剂尼莫地平和NMDA受体拮抗剂MK 801，测试其预防咖啡因或乙醇给药引起的攻击的能力。尼莫地平阻断了咖啡因和乙醇诱导的攻击，而MK 801对压力和咖啡因诱导的攻击有效。这些结果支持了一个共同的作用，过度的神经元兴奋性和增加钙内流的攻击引发的不同代理。总之，这些结果表明，蹒跚小鼠是一种新的模型，以调查触发发作性神经系统疾病。(C)2002年爱思唯尔科技有限公司All rights reserved.
Mutations in ion channels, or channelopathies, often lead to neurological disorders in which normal behavior is interrupted by attacks of debilitating symptoms such as pain, weakness or abnormal motor control. Attacks are often precipitated by similar stimuli, including stress, caffeine, ethanol, exercise or fatigue. The tottering mouse inherits a mutation in P/Q-type calcium channels and reliably exhibits attacks of Abnormal movements, or dyskinesia. To determine if this mouse mutant is an appropriate model to study episodic neurological disorders, tottering mice were exposed to different enviromnental conditions or drugs known to precipitate attacks in humans. Stress, caffeine and ethanol all reliably induced attacks in tottering mice. Since calcium influx has previously been implicated in stress-induced tottering mouse attacks, the L-type calcium channel antagonist, nimodipine, and the NMDA receptor antagonist, MK 801, were tested for their ability to prevent attacks caused by caffeine or ethanol administration. Nimodipine blocked both caffeine- and ethanol-induced attacks, while MK 801 was effective against stress- and caffeine-induced attacks. These results support a common role for excess neuronal excitability and increased calcium influx in attacks triggered by diverse agents. Together, these results suggest that the tottering mouse is a novel model to investigate triggers of episodic neurological disorders. (C) 2002 Elsevier Science Inc. All rights reserved.