NO RELATED MODULATION OF CARDIAC CALCIUM CHANNELS

心脏钙通道无相关调节

• 批准号: 6024296
• 负责人: DONALD Leroy CAMPBELL
• 金额: $ 22.19万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6024296
• 关键词: calcium channel; cardiac myocytes; ferrets; guanylate cyclase; intracellular transport; myocardium; neuromuscular transmission; nitric oxide; oxidation reduction reaction; protein localization; sarcolemma; thiols; tissue /cell culture; voltage /patch clamp

DESCRIPTION (adapted from the applicant's abstract): The general hypotheses to be tested are: 1) NO and RSNOs/OONO- (exemplary protein thiol NO+donating and oxidizing agents, respectively) can modulate L-type calcium current (IcaL) by two distinct mechanisms: i) an indirect mechanism involving activation of soluble guanylyl cyclase (NO); and ii) a direct mechanism involving either S-nitrosylation (RSNOs) or oxidation (RSNOs/OONO-) of critical thiol groups in sarcolemmal and/or extracellularly accessible "redox switches" located either in the L-channel subunit complex or an associated regulatory molecule(s); 2) Specific cellular mechanisms underlying these effects may vary significantly among different cardiac myocyte types (working versus pacemaking myocytes); and 3) Cellular redox state of critical thiols located in the sarcolemmal/ extracellular redox switches is an important determinant in both modulation of cardiac ICaL and in the response "NO". These issues will be addressed using a combination of patch clamp techniques (both whole cell and single channel) to study native IcaL in ferret enzymatically isolated myocytes (ventricle, SA node) and molecular biological techniques (immunolocalization, in situ hybridization) to determine the tissue, cellular and subcellular correlates underlying the functional effects of NO- and redox-related modulation of IcaL.

描述（改编自申请人的摘要）：一般假设