Stress without distress: homeostatic role for KATP channels
Stress without distress: homeostatic role for KATP channels
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DOI：
10.1038/sj.mp.4001323
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发表时间：
2003-03
影响因子：
11
通讯作者：
L. Zingman;D. Hodgson;A. Alekseev;A. Terzic
中科院分区：
文献类型：
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作者：
L. Zingman;D. Hodgson;A. Alekseev;A. Terzic
压力被定义为对生存所需的狭窄生理参数的真实或暗示的威胁，存在的动态包括一系列持续的压力事件及其后果。 1 自我保护是通过一般适应综合症来实现的，这种适应综合症是由大脑对威胁的识别引发的，从而导致行为改变以及下丘脑-垂体-肾上腺轴和自主神经系统的激活。 1 这种普遍存在的反应是“战斗或逃跑”反应的基础，通过改变身体功能来维持对抗或逃避威胁条件所需的新的表现水平。 1 然而，性能的增强对新陈代谢的要求很高，并且需要一种安全机制来防止资源的致命耗尽。最近，ATP敏感钾（KATP）通道，一种细胞膜代谢传感器，被认为是在对压力的适应性反应过程中维持身体稳态的关键组成部分，这样反应本身不会对生物体有害。 2KATP 通道广泛存在于代谢活跃的组织中，是通过成孔内向整流钾通道 Kir6 的物理结合而形成的。 x，具有调节性磺酰脲受体，SUR。 3 就这样，Kir6. 2 和 SUR2A 生成心脏和骨骼肌 KATP 通道。 4 代谢传感通过 Kir6 的调节发生。 2 SUR2A 亚基 ATP 酶活性对 ATP 敏感，因此 SUR2A 在水解后状态的稳定有利于 K+ 通过 Kir6 流出。 2导致膜超极化。 5 这些内在通道特性以及 KATP 通道蛋白与细胞代谢途径的紧密整合，负责膜电位依赖性细胞功能的快速、精确的代谢调节。 5 个血管平滑肌通道结合 Kir6。胰腺β细胞中的通道1和SUR2B、6和通道组成Kir6。 2 和 SUR1。 3 在神经元中，Kir6 的各种排列。 1 或 Kir6。 2和SUR1或SUR2共表达形成KATP通道。 7 这种结构多样性定义了 KATP 通道广泛参与组织特异性功能。
Stress is defined as a threat, real or implied, to the narrow range of physiological parameters necessary for survival, with the dynamic of existence comprising an ongoing sequence of stressful events and their consequences. 1 Self-preservation is achieved through the general adaptation syndrome that is initiated by brain recognition of threat leading to modification of behavior and activation of the hypothalamic-pituitary–adrenal axis and autonomic nervous system. 1 This ubiquitous response underlies the ‘fight-orflight’reaction by alteration of bodily functions to sustain a new performance level necessary for confrontation or evasion of threatening conditions. 1 However, augmentation in performance is metabolically demanding, and requires a safety mechanism to prevent fatal exhaustion of resources. Recently, the ATP-sensitive potassium (KATP) channel, a cell membrane metabolic sensor, was identified as a critical component in maintaining the body’s homeostasis during the adaptive reaction to stress, such that the reaction itself does not become deleterious to the organism. 2KATP channels, widely represented in metabolically active tissues, are formed through physical association of the pore-forming inwardly rectifying potassium channel, Kir6. x, with the regulatory sulfonylurea receptor, SUR. 3 In this way, Kir6. 2 and SUR2A generate cardiac and skeletal muscle KATP channels. 4 Metabolic sensing occurs through modulation of Kir6. 2 ATP-sensitivity by the SUR2A subunit ATPase activity such that stabilization of SUR2A in a posthydrolytic state favors K+ efflux through Kir6. 2 leading to membrane hyperpolarization. 5 These intrinsic channel properties, along with tight integration of KATP channel proteins with cellular metabolic pathways, are responsible for the rapid and precise metabolic modulation of membrane potential-dependent cellular functions. 5 Vascular smooth muscle channels combine Kir6. 1 and SUR2B, 6 and channels in pancreatic β-cells comprise Kir6. 2 and SUR1. 3 In neurons, various permutations of Kir6. 1 or Kir6. 2 and SUR1 or SUR2 coexpression form KATP channels. 7 Such structural diversity defines a wide spectrum of KATP channel involvement in tissue-specific func-