Noradrenergic blockade prevents attacks in a model of episodic dysfunction caused by a channelopathy
Noradrenergic blockade prevents attacks in a model of episodic dysfunction caused by a channelopathy
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DOI：
10.1016/j.nbd.2005.03.004
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发表时间：
2005-11-01
影响因子：
6.1
通讯作者：
Hess, EJ
中科院分区：
文献类型：
--
作者：
Fureman, BE;Hess, EJ
发作性神经功能障碍通常由离子通道基因突变引起。尽管知道突变，但导致通道病发作的因素尚不清楚。在人类中，钙通道基因CA CNA 1A的突变与家族性偏瘫性偏头痛和发作性共济失调2型的神经功能障碍发作有关。在步履蹒跚的老鼠中，同一基因的突变导致类似于阵发性运动障碍的发作。压力，一种与人类偶发性疾病相关的触发因素，可靠地激发了蹒跚小鼠的发作。由于去甲肾上腺素能神经传递对应激反应至关重要，并且由于在蹒跚小鼠中观察到去甲肾上腺素能神经支配过度，因此研究了去甲肾上腺素在应激诱导的发作中的作用。作用于α-肾上腺素能受体以阻断去甲肾上腺素能传递的药物可预防发作。然而，促进去甲肾上腺素能神经传递的药物未能诱导发作。这些结果表明，虽然去甲肾上腺素能神经传递可能是必要的攻击，增加去甲肾上腺素是不足以诱导攻击。(c)2005年爱思唯尔公司All rights reserved.
Episodic neurological dysfunction often results from ion channel gene mutations. Despite knowledge of the mutations, the factors that precipitate attacks in channelopathies are not clear. In humans, mutations of the calcium channel gene CA CNA1A are associated with attacks of neurological dysfunction in familial hemiplegic migraine and episodic ataxia type-2. In tottering mice, a mutation in the same gene causes attacks resembling paroxysmal dyskinesia. Stress, a trigger associated with human episodic disorders, reliably elicits attacks in tottering mice. Because noradrenergic neurotransmission is critical to the stress response and because noradrenergic hyperinnervation is observed in tottering mice, the role of norepinephrine in stress-induced attacks was investigated. Drugs that act at alpha-adrenergic receptors to block noradrenergic transmission prevented attacks. However, agents that facilitate noradrenergic neurotransmission failed to induce attacks. These results suggest that, while noradrenergic neurotransmission may be necessary for attacks, an increase in norepinephrine is not sufficient to induce attacks. (c) 2005 Elsevier Inc. All rights reserved.