Increased motor drive and sleep loss in mice lacking Kv3-type potassium channels
Increased motor drive and sleep loss in mice lacking Kv3-type potassium channels
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DOI：
10.1046/j.1601-183x.2003.00054.x
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发表时间：
2004-04-01
影响因子：
2.5
通讯作者：
Joho, RH
中科院分区：
文献类型：
--
作者：
Espinosa, F;Marks, G;Joho, RH
电压门控钾通道Kv3.1和Kv3.3在大脑中广泛表达，包括涉及运动活动控制的区域和被认为调节唤醒状态的区域。虽然Kv3.1和Kv3.3-单突变体显示出一些生理变化，但先前的研究揭示了相对微妙的行为改变，表明Kv3.1和Kv3.3通道亚基可能由一对冗余基因编码。与这一假设相一致，Kv3.1/Kv3.3缺陷型小鼠在暴露于新环境时表现出“强”突变表型，包括运动功能障碍（共济失调、肌阵挛、震颤）和多动。在本文中，我们报告，Kv3.1/Kv3.3缺陷型小鼠也组成性多动。与野生型小鼠相比，双突变体显示出“不安”，这在小鼠正常休息时的光照期特别突出，其特征是走动和刻板活动增加一倍以上，并伴有40%的睡眠减少。当我们重新调查这两个单一的突变体，我们观察到组成性增加的走动和刻板的活动与睡眠丧失Kv3.1-单一的突变体，但不是在Kv3.3-单一的突变体。这些发现表明，Kv3.1通道亚基的缺乏是导致运动驱动增加和睡眠时间减少的主要原因。
The voltage-gated potassium channels Kv3.1 and Kv3.3 are widely expressed in the brain, including areas implicated in the control of motor activity and in areas thought to regulate arousal states. Although Kv3.1 and Kv3.3-single mutants show some physiological changes, previous studies revealed relatively subtle behavioral alterations suggesting that Kv3.1 and Kv3.3 channel subunits may be encoded by a pair of redundant genes. In agreement with this hypothesis, Kv3.1/Kv3.3-deficient mice display a 'strong' mutant phenotype that includes motor dysfunction (ataxia, myoclonus, tremor) and hyperactivity when exposed to a novel environment. In this paper we report that Kv3.1/Kv3.3-deficient mice are also constitutively hyperactive. Compared to wildtype mice, double mutants display 'restlessness' that is particularly prominent during the light period, when mice are normally at rest, characterized by more than a doubling of ambulatory and stereotypic activity, and accompanied by a 40% sleep reduction. When we reinvestigated both single mutants, we observed constitutive increases of ambulatory and stereotypic activity in conjunction with sleep loss in Kv3.1-single mutants but not in Kv3.3-single mutants. These findings indicate that the absence of Kv3.1-channel subunits is primarily responsible for the increased motor drive and the reduction in sleep time.