REGULATION OF THE CARDIAC NA+/CA+2 EXCHANGER

心脏 NA /CA 2 交换器的调节

• 批准号: 2714041
• 负责人: JOHN Paul REEVES
• 金额: $ 25.97万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-06-01 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2714041
• 关键词: CHO cells; adenosine triphosphate; calcium channel; calcium flux; calcium indicator; calcium ion; cell morphology; gramicidin; heart contraction; intermediate filaments; ion transport; ionomycin; ionophores; membrane transport proteins; phosphatase inhibitor; site directed mutagenesis; sodium channel; sodium ion

In this project, the applicant will investigate the regulation of Na+/Ca2+ exchange activity in transfected Chinese hamster ovary cells that permanently express either the wild-type cardiac Na+/Ca2+ exchanger or mutant exchangers created by site-directed mutagenesis. The cental hypothesis is that exchange activity in intact cells is regulated at three different levels of complexity: (1) throughkinetic alterations induced by changes in cytosolic (Ca2+), (2) through interactions with the cytoskeleton, and (3) through interactions with Ca2+ sequestering organelles. The applicant will characterize the regulation of exchange activity by cytosolic (Na+), (Ca2+), and pH by measuring exchange-mediated Ba2+ influx in cells treated with the ionophores gramicidin and ionomycin. The applicant will also examine the influence of exchange activity of cytoskeletal changes induced by the phosphatase inhibitor calyculin A, and by osmotic shrinkage, with special emphasis on the role of intermediate filaments in the response. Finally, the applicant will use selective inhibitors and Ca2+ leading/depletion protocols to examine the role of Ca2+ uptake and release by the endoplasmic reticulum and otehr Ca2+ sequestering organelles in activating or deactivating exchange activity.

在这个项目中，申请人将调查的监管