STRUCTURE AND FUNCTION OF MAMMALIAN POTASSIUM CHANNELS

哺乳动物钾通道的结构和功能

• 批准号: 3415038
• 负责人: JOHN P ADELMAN
• 金额: $ 20.6万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-02-01 至 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3415038
• 关键词: Amphibia; chemical structure function; divalent cations; egg /ovum; electrophysiology; laboratory rat; molecular cloning; molecular dynamics; pharmacokinetics; polymerase chain reaction; potassium channel; single cell analysis; site directed mutagenesis; tetraethylammonium compound

The functions of potassium channels are central to the properties of all excitable mammalian cells. Electrophysiological and pharmacokinetic studies have defined many different classes of potassium channels. However, the molecular basis of this diversity, and the relationships between channel structure and function remain unknown. Through the use of molecular cloning and electrophysiology, we have isolated, characterized, and expressed in frog oocytes a mammalian potassium channel from rat hippocampus. Surprisingly, the properties of this channel do not fit any single kind of channel as defined by classical methods. The major goal of the research proposed here is to further our understanding of the molecular basis of variations among the different classes of mammalian potassium channels. First, we will clone, characterize, and express in frog oocytes mammalian potassium channels, both voltage and ligand gated, with distinct structural and functional properties. The different kinds of channels will be compared to those known by classical methods. Second, structure-function studies, using site directed mutagenesis, will be performed using a range of potassium channels with distinct properties. Site directed mutant studies of whole, reconstructed channels will be conducted in oocytes. Third, ancillary factors which may influence channel functions will be investigated. Fourth, subunit-specific probes will be generated, based on established nucleotide sequences, and employed in in situ hybridization studies to map the expression patterns of potassium channels in the brain. By studying the structure and function of mammalian potassium channels in this way, we hope to answer questions regarding the molecular basis of potassium channel diversity and the significance of this diversity to the basic properties of excitable mammalian cells.