Behavioral phenotyping of mice lacking the KATP channel subunit Kir6.2

Behavioral phenotyping of mice lacking the KATP channel subunit Kir6.2
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DOI:
10.1016/j.physbeh.2006.01.013
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发表时间:
2006-04-15
影响因子:
2.9
通讯作者:
Liss, B
Liss, B
中科院分区:
医学3区
文献类型:
--
作者:
Deacon, RMJ;Brook, RC;Liss, B

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atp敏感钾(K-ATP)通道在各种组织和细胞类型中表达,它们作为所谓的代谢传感器,将代谢状态与细胞兴奋性相结合。大多数K-ATP通道类型的孔是由Kir6.2亚基构建的。对Kir6.2基因敲除(KO)小鼠的分析发现,在代谢需求的情况下,中枢和外周K-ATP通道具有多种不同的功能作用。然而,这些通道的广泛分布表明,它们可能在代谢控制条件下影响细胞生理和动物行为。由于Kir6.2 KO小鼠在生理控制条件下尚未进行全面的行为描述,我们对Kir6.2 KO和相应的野生型(WT)小鼠进行了测试电池,以评估情绪行为、运动活动和协调、物种典型行为和认知。结果表明,在这些测试情况下,Kir6.2 KO小鼠活动较少,运动协调受损,并且在情绪反应方面与对照组不同。在类似家庭笼环境的测试环境中,KO和WT小鼠之间的差异通常减弱。此外,在他们的家笼中,KO小鼠比WT小鼠更活跃。因此,我们的研究结果表明,在代谢控制条件下,含kir6.2的K-ATP通道的缺失确实会影响动物的行为,尤其是在新的情况下。这些发现为K-ATP通道赋予了超越先前描述的新功能角色。然而,根据K-ATP通道的广泛表达,这些影响是复杂的,取决于测试设备,程序和先前经验的细节。(c) 2006爱思唯尔公司版权所有。
ATP-sensitive potassium (K-ATP) channels are expressed in various tissues and cell-types where they act as so-called metabolic sensors that couple metabolic state to cellular excitability. The pore of most K-ATP channel types is built by Kir6.2 subunits. Analysis of a general Kir6.2 knockout (KO) mouse has identified a variety of different functional roles for central and peripheral K-ATP channels in situations of metabolic demand. However, the widespread distribution of these channels suggests that they might influence cellular physiology and animal behavior under metabolic control conditions. As a comprehensive behavioral description of Kir6.2 KO mice under physiological control conditions has not yet been carried out, we subjected Kir6.2 KO and corresponding wild-type (WT) mice to a test battery to assess emotional behavior, motor activity and coordination, species-typical behaviors and cognition. The results indicated that in these test situations Kir6.2 KO mice were less active, had impaired motor coordination, and appeared to differ from controls in their emotional reactivity. Differences between KO and WT mice were generally attenuated in test situations that resembled the home cage environment. Moreover, in their home cages KO mice were more active than WT mice. Thus, our results suggest that loss of Kir6.2-containing K-ATP channels does affect animal behavior under metabolic control conditions, especially in novel situations. These findings assign novel functional roles to K-ATP channels beyond those previously described. However, according to the widespread expression of K-ATP channels, these effects are complex, being dependent on details of test apparatus, procedure and prior expenence. (c) 2006 Elsevier Inc. All rights reserved.