Xu Jianchao, Koni Pandelakis A, Wang Peili, Li Guoyong, Kaczmarek Leonard, Wu Yanling, Li Yanyan, Flavell Richard A, Desir Gary V
Department of Medicine, Yale University School of Medicine, New Haven, CT 06520-8029, USA.
Hum Mol Genet. 2003 Mar 1;12(5):551-9. doi: 10.1093/hmg/ddg049.
Voltage-gated potassium (Kv) channels regulate cell membrane potential and control a variety of cellular processes. Kv1.3 channels are expressed in several tissues and believed to participate in cell volume regulation, apoptosis, T cell activation and renal solute homeostasis. Examination of Kv1.3-deficient mice (Kv1.3(-/-)), generated by gene targeting, revealed a previously unrecognized role for Kv1.3 in body weight regulation. Indeed, Kv1.3(-/-) mice weigh significantly less than control littermates. Moreover, knockout mice are protected from diet-induced obesity and gain significantly less weight than littermate controls when placed on a high-fat diet. While food intake did not differ significantly between Kv1.3(-/-) and controls, basal metabolic rate, measured at rest by indirect calorimetry, was significantly higher in knockout animals. These data indicate that Kv1.3 channels may participate in the pathways that regulate body weight and that channel inhibition increases basal metabolic rate.
电压门控钾（Kv）通道调节细胞膜电位并控制多种细胞过程。Kv1.3通道在多种组织中表达，据信参与细胞体积调节、细胞凋亡、T细胞活化和肾溶质稳态。通过基因靶向产生的Kv1.3缺陷小鼠（Kv1.3(-/-)）的研究揭示了Kv1.3在体重调节中以前未被认识的作用。事实上，Kv1.3(-/-)小鼠的体重明显低于同窝对照小鼠。此外，基因敲除小鼠对饮食诱导的肥胖具有抵抗力，当置于高脂饮食中时，其体重增加明显少于同窝对照小鼠。虽然Kv1.3(-/-)小鼠与对照小鼠的食物摄入量没有显著差异，但通过间接量热法在静息状态下测量的基础代谢率在基因敲除动物中显著更高。这些数据表明，Kv1.3通道可能参与调节体重的途径，并且通道抑制会增加基础代谢率。
