POTASSIUM HOMEOSTASTASIS OF KV 1.3-DEFICIENT MICE

说明(改编自应用程序) 钾稳态的紊乱会导致致命的后果，如 心脏骤停。肾脏是维持血钾的重要器官。 集中在一个非常窄的范围内。为了实现这一点，肾上皮细胞 都配备了膜转运体，如Na-ATPase和K通道。这个 肾脏对钾的吸收和分泌的确切机制尚不完全 然而，理解，最近的进展表明钾通道可能起作用 在这一过程中发挥重要作用。 除了内向整流K通道外，电压门控K通道还 在肾脏中表达。加里·德塞尔博士的实验室已经发现了几个这样的 频道。其中两个已经被广泛描述：Kv1.3和KCNA10。 尽管这些通道在肾脏钾离子通道中的确切生理作用 动态平衡尚不清楚，推测Kv1.3与 ATP敏感的KATP通道，介导K退出到K可以进入的间质 通过以下方式返回到血液中或积累并循环回细胞 Na+，K+-ATPase泵。KCNA10可能参与K转运，调节 血管张力、心脏动作电位和皮质醇分泌。 为了验证这些假设，我将研究Kv1.3的亚细胞定位 在肾上皮细胞中，并研究Kv1.3在体内的功能 基因打靶。该项目的具体目标是：(1)Kv1.3的本地化 在肾上皮细胞中。(2)Kv1.3基因缺陷小鼠的建立。(3) K0.3基因缺陷小鼠的特征。(4)KCNA10基因敲除的产生 小鼠和Kv1.3/KCNA10双基因敲除小鼠。

DESCRIPTION (adapted from the application) Disturbances of potassium homeostasis can result in fatal consequences such as cardiac arrest. The kidney is a vital organ that maintains serum potassium concentration in a very narrow range. To achieve this, renal epithelial cells are equipped with membrane transporters such as Na-ATPase and K channels. The exact mechanism of K absorption and secretion in the kidney is not completely understood, however, recent progress suggests that potassium channels may play an important role in the process. In addition to inward rectifier K channels, voltage-gated K channels are also expressed in kidney. Dr. Gary Desir's laboratory has identified several such channels. Two of these have been extensively characterized: Kv1.3 and KCNA10. Although the precise physiological role of these channels in renal K homeostasis is unclear, it is postulated that Kv1.3, in conjunction with ATP-sensitive KATP channels, mediates K exit into interstitium where K can be returned to blood stream or accumulated and recycled back into the cell by Na+,K+-ATPase pump. KCNA10 may participate in K transport, the regulation of vascular tone, the cardiac action potential, and cortisol secretion. To test these hypotheses, I will examine the sub-cellular localization of Kv1.3 in the renal epithelia, and study the Kv1.3 function in vivo using gene-targeting. The Specific Aims of the project are: (1) Localization of Kv1.3 in renal epithelial cells. (2) Generation of Kv1.3-deficient mice. (3) Characterization of the K0.3-deficient mice. (4) Generation of KCNA10 knockout mouse and Kv1.3/KCNA10 double knockout mouse.