Emerging roles for two-pore-domain potassium channels and their potential therapeutic impact.
Emerging roles for two-pore-domain potassium channels and their potential therapeutic impact.
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DOI：
10.1016/j.tips.2008.07.013
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发表时间：
2008-11
影响因子：
13.8
通讯作者：
Barrett PQ
中科院分区：
文献类型：
--
作者：
Bayliss DA;Barrett PQ
广泛分布和良好调节的双孔域背景钾（K2P）通道的独特基因家族建立静息膜电位和细胞兴奋性。通过使用删除kp通道基因的新小鼠模型，这些通道对重要生理功能的贡献现在被揭示出来。在这里，我们强调了最近的研究结果，这些研究使用小鼠删除了k2 -通道亚基，揭示了这些通道的生理功能，主要是TASK和TREK亚群。与挥发性麻醉剂激活这些K2P通道一致，TASK-1、TASK-3和TREK-1有助于麻醉诱导的催眠和固定。尽管在呼吸相关神经元中广泛表达，但脑干对二氧化碳或pH值呼吸的控制并不需要酸敏感的TASK通道。然而，TASK通道对于肾上腺醛固酮分泌的稳态调节是必要的。热，拉伸和脂质激活的TREK-1通道有助于温度和机械疼痛感觉，多不饱和脂肪酸的神经保护，以及意想不到的情绪调节。碱激活的TASK-2通道是肾近端小管细胞HCO3-重吸收和渗透体积调节所必需的。开发选择性调节K2P通道的化合物对于验证这些结果和评估针对这些有趣通道的治疗效果至关重要。
A distinct gene family of widely distributed and well-modulated two-pore-domain background potassium (K2P) channels establish resting membrane potential and cell excitability. By using new mouse models in which K2P-channel genes are deleted, the contributions of these channels to important physiological functions are now being revealed. Here, we highlight results of recent studies using mice deleted for K2P-channel subunits that uncover physiological functions of these channels, mostly those of the TASK and TREK subgroup. Consistent with activation of these K2P channels by volatile anesthetics, TASK-1, TASK-3 and TREK-1 contribute to anesthetic-induced hypnosis and immobilization. The acid-sensitive TASK channels are not required for brainstem control of breathing by CO2 or pH, despite widespread expression in respiratory-related neurons. TASK channels are necessary, however, for homeostatic regulation of adrenal aldosterone secretion. The heat-, stretch- and lipid-activated TREK-1 channels contribute to temperature and mechanical pain sensation, neuroprotection by polyunsaturated fatty acids and, unexpectedly, mood regulation. The alkaline-activated TASK-2 channel is necessary for HCO3- reabsorption and osmotic volume regulation in kidney proximal tubule cells. Development of compounds that selectively modulate K2P channels is crucial for verifying these results and assessing the efficacy of therapies targeting these interesting channels.
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影响因子：
11.4
作者：
Heitzmann, Dirk;Derand, Renaud;Barhanin, Jacques
通讯作者：
Barhanin, Jacques
影响因子：
3.5
作者：
Karschin, C;Wischmeyer, E;Karschin, A
通讯作者：
Karschin, A
DOI：
10.1016/s0034-5687(01)00288-2
发表时间：
2001-12-01
期刊：
RESPIRATION PHYSIOLOGY
影响因子：
--
作者：
Bayliss, DA;Talley, EM;Lei, QB
通讯作者：
Lei, QB
DOI：
10.1152/ajprenal.00132.2006
发表时间：
2007-02-01
影响因子：
4.2
作者：
L'Hoste, S.;Barriere, H.;Poujeol, P.
通讯作者：
Poujeol, P.
影响因子：
20.1
作者：
Blondeau, Nicolas;Petrault, Olivier;Heurteaux, Catherine
通讯作者：
Heurteaux, Catherine