Mutant Analysis of a Novel High Conductance K+ Channel

新型高电导 K 通道的突变分析

• 批准号: 6681127
• 负责人: LAWRENCE B SALKOFF
• 金额: $ 30.98万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6681127
• 关键词: Caenorhabditis elegans; Xenopus oocyte; cooperative study; electrophysiology; gene expression; hypoxia; immunocytochemistry; laboratory rat; neurons; polymerase chain reaction; potassium channel; site directed mutagenesis; tissue /cell culture; voltage /patch clamp; voltage gated channel

DESCRIPTION (provided by applicant): A comparative genomic approach, which began with the analysis of the unusual slo-2 gene in C. elegans has led to the molecular identification of the long sought-after mammalian Na+-activated potassium channel (KNa). KNa channels have been identified in cardiomyocytes and neurons where they may serve as an important protective mechanism against ischemia (Dryer, 1994). Our studies showed that the C. elegans gene, slo-2, also confers resistance to hypoxia (Yuan et al, submitted). Our studies further showed that mammalian KNa channels are encoded by the rSlack gene (Joiner, et al, 1998) (rslo2), a mammalian orthologue of the C. elegans slo-2 gene. We showed that rSLO-2 channels have all the properties of native KNa channels. We now plan to follow up on these findings by investigating the role of SLO-2 channels in different classes of identified neurons (in C. elegans), cloning and functionally characterizing two distinct mammalian slo-2 genes present in human (and mouse) genomes, and defining the structural regions in mammalian SLO-2 channels which are responsible for the salient property of sensing Na + and CI-. In addition to extending our theoretical understanding of the factors involved in ion channel activation, this information may be important for clinical applications. Pharmacological agents which modulate the KNa channel, especially channel openers, might serve a useful role in preventing cell damage during cardiac ischemia and stroke, and may serve as a protective agent in the pretreatment of organs used in transplant procedures.

描述（由申请人提供）：一种比较基因组方法，始于对秀丽隐杆线虫中不寻常的SLO-2基因的分析，这导致了长期受欢迎的哺乳动物Na+活化钾通道（KNA）的分子鉴定。在心肌细胞和神经元中已经鉴定出KNA通道，它们可能是针对缺血的重要保护机制（Dryer，1994）。我们的研究表明，秀丽隐杆线虫基因SLO-2也赋予对缺氧的抗药性（Yuan等人，提交）。我们的研究进一步表明，哺乳动物KNA通道由RSLACK基因编码（Joiner等，1998）（RSLO2）（RSLO2），这是秀丽隐杆线虫C. elegans slo-2基因的哺乳动物直系同源物。我们表明RSLO-2通道具有天然KNA通道的所有特性。现在，我们计划通过调查SLO-2通道在不同类别的神经元（以秀丽隐杆线虫）的作用，克隆和功能表征的两个不同的哺乳动物SLO-2基因的作用来跟进这些发现，并在人（和小鼠）基因组中表征存在两个不同的哺乳动物SLO-2基因，并在哺乳动物SLO-2通道中定义了具有Salient Naient Property of Naient of Naient of Sentient naient of Senting Naient and + Cii的结构区域的结构区域。除了扩展我们对离子通道激活中涉及的因素的理论理解外，此信息对于临床应用可能很重要。 调节KNA通道，尤其是通道开瓶器的药理学剂可能在预防心脏缺血和中风期间细胞损伤方面发挥有用的作用，并且可以在移植程序中使用的器官预处理中作为保护剂。