Mirkovic Kelsey, Palmersheim Jaime, Lesage Florian, Wickman Kevin
Department of Pharmacology, University of Minnesota Minneapolis, MN, USA.
Front Behav Neurosci. 2012 Sep 7;6:60. doi: 10.3389/fnbeh.2012.00060. eCollection 2012.
Two-pore domain K(+) (K(2P)) channels are thought to underlie background K(+) conductance in many cell types. The Trek subfamily of K(2P) channels consists of three members, Trek1/Kcnk2, Trek2/Kcnk10, and Traak/Kcnk4, all three of which are expressed in the rodent CNS. Constitutive ablation of the Trek1 gene in mice correlates with enhanced sensitivity to ischemia and epilepsy, decreased sensitivity to the effects of inhaled anesthetics, increased sensitivity to thermal and mechanical pain, and resistance to depression. While the distribution of Trek2 mRNA in the CNS is broad, little is known about the relevance of this Trek family member to neurobiology and behavior. Here, we probed the effect of constitutive Trek2 ablation, as well as the simultaneous constitutive ablation of all three Trek family genes, in paradigms that assess motor activity, coordination, anxiety-related behavior, learning and memory, and drug-induced reward-related behavior. No differences were observed between Trek2(-/-) and Trek1/2/Traak(-/-) mice in coordination or total distance traveled in an open-field. A gender-dependent impact of Trek ablation on open-field anxiety-related behavior was observed, as female but not male Trek2(-/-) and Trek1/2/Traak(-/-) mice spent more time in, and made a greater number of entries into, the center of the open-field than wild-type counterparts. Further evaluation of anxiety-related behavior in the elevated plus maze and light/dark box, however, did not reveal a significant influence of genotype on performance for either gender. Furthermore, Trek(-/-) mice behaved normally in tests of learning and memory, including contextual fear conditioning and novel object recognition, and with respect to opioid-induced motor stimulation and conditioned place preference (CPP). Collectively, these data argue that despite their broad distribution in the CNS, Trek channels exert a minimal influence on a wide-range of behaviors.
双孔结构域钾离子（K(2P)）通道被认为是多种细胞类型中背景钾离子电导的基础。K(2P)通道的Trek亚家族由三个成员组成，即Trek1/Kcnk2、Trek2/Kcnk10和Traak/Kcnk4，这三个成员在啮齿动物的中枢神经系统中均有表达。小鼠中Trek1基因的组成性缺失与对缺血和癫痫的敏感性增强、对吸入麻醉药作用的敏感性降低、对热痛和机械痛的敏感性增加以及对抑郁的抵抗力有关。虽然Trek2 mRNA在中枢神经系统中的分布广泛，但对于这个Trek家族成员与神经生物学和行为的相关性知之甚少。在这里，我们在评估运动活动、协调性、焦虑相关行为、学习和记忆以及药物诱导的奖赏相关行为的范式中，探究了Trek2组成性缺失以及所有三个Trek家族基因同时组成性缺失的影响。在旷场实验中，Trek2基因敲除小鼠（Trek2(-/-)）和Trek1/2/Traak基因敲除小鼠（Trek1/2/Traak(-/-)）在协调性或总移动距离方面没有观察到差异。观察到Trek基因敲除对旷场焦虑相关行为有性别依赖性影响，因为雌性而非雄性的Trek2(-/-)和Trek1/2/Traak(-/-)小鼠在旷场中心停留的时间更长，进入中心的次数更多，比野生型对照组多。然而，在高架十字迷宫和明暗箱中对焦虑相关行为的进一步评估并未发现基因型对任何性别的行为表现有显著影响。此外，Trek基因敲除小鼠在学习和记忆测试中表现正常，包括情境恐惧条件反射和新物体识别，以及在阿片类药物诱导的运动刺激和条件性位置偏爱（CPP）方面。总体而言，这些数据表明，尽管Trek通道在中枢神经系统中分布广泛，但对广泛的行为影响极小。
