STRUCTURE AND FUNCTION OF THE TOK1 POTASSIUM CHANNEL

TOK1 钾通道的结构和功能

• 批准号: 2444897
• 负责人: Steve A N Goldstein
• 金额: $ 35.61万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2444897
• 关键词: Caenorhabditis elegans; Xenopus; Xenopus oocyte; ammonium compounds; barium; cadmium; calcium; cesium; complementary RNA; gene mutation; magnesium; molecular cloning; pharmacology; potassium; potassium channel; protein structure function; rubidium; site directed mutagenesis; vesicle /vacuole; voltage /patch clamp; yeasts; zinc

TOK1 is the first member of a new family of k+ channels [1]. The channel, which we cloned from the budding yeast Saccharomyces cerevisiae, has two novel features. First, it is structurally distinct. In contrast to previously identified K= channel alpha-subunits which bear only one pore- forming P domain, TOK1 has two. Second, TOK1 is the first example of a new functional type of K+-selective channel, an "outward rectifier'. Like inward rectifier superfamily channels, TOK1 'activation' is coupled to the equilibrium potential for potassium (EK), but TOK1 passes K+ current in the outward direction, a previously undescribed channel phenotype. Our overall goal in this work is to detail the basic attributes of TOK1 channels and where possible, elucidate their structural basis,. Our 6 specific aims for the next 5 years are: (1) to detail basic single channel properties of TOK1 channels; (2) to investigate the molecular mechanism underlying TOK1 outward rectification; (3) to evaluate function of the 2 P domains in the intact channel and when each of the P domains is expressed separately; (4) to study the membrane topology of the channel with emphasis on the relative arrangement of its 2 P domains; (5) to clone homologues of the channel from higher organism; and, (6) to apply the tools of yeast molecular genetics to study of TOK1 potassium channel structure and function. Preliminary findings are presented to support the feasibility of each of these aims using macroscopic and single channel recording of TOK1 channels expressed in Xenopus laevis oocytes and standard molecular genetic tools.

TOK1是k+通道[1]新家族的第一个成员。的频道,