TRANSMITTER MODULATION OF REPOLARIZATION IN HEART

心脏复极的发射机调制

• 批准号: 3472237
• 负责人: ERWIN F SHIBATA
• 金额: $ 9.72万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3472237
• 关键词: Anura; acetylcholine; adrenergic receptor; arrhythmia; atrium; biological models; cholera toxin; cholinergic agents; heart Purkinje's fiber; heart conduction system; heart pharmacology; isoproterenol; laboratory rabbit; myocardium; neurotransmitters; phospholipase C; phosphorylation

Time - and voltage-dependent K+ currents in heart are of fundamental importance in the development of the pacemaker potential, in triggering and controlling repolarization and in the responses of the heart to various autonomic transmitters and other pharmacologic agents. In spite of this, quantitative information concerning the number, the time-course, and the size(s) of K+ currents in mammalian heart is not complete. In this proposal, previous work on K+ currents will be extended, by further exploring the nature and the possible second messengers of the potassium current induced by muscarinic agonists, and by identifying the types of potassium current present in a mammalian model for human myocardium: the rabbit atrium. In these experiments, single cells obtained by enzymatic dispersion from bullfrog atrium or rabbit atrium will be used and both whole-cell voltage clamp recordings and single channel patch clamp recordings will be made. In addition, attempts will be made to "hold" populations of cells using short-term incubation techniques so that pre-treatment with biochemical pathway inhibitors can be carried out in certain stages of the work. Success in the proposed experiments will yield new data further defining the mechanism by which muscarinic agonists inhibits isoproterenol-induced current changes, and providing quantitative information concerning details of repolarization in the rabbit atrium. In all physiological states and certain pathological conditions adrenergic tone is present and can be modulated by a variety of mechanisms, including changes in cholinergic nerve activity. These results will be of considerable pharmacological and pathophysiological importance in the understanding and control of arrythmias.

心脏的时间和电压依赖性K+电流是 起搏器发展的根本重要性 电位，在触发和控制复极和在 心脏对各种自主神经递质的反应， 其他药物。 尽管如此，量化 关于数量、时间进程和 哺乳动物心脏中K+电流的大小并不完整。 在这 建议，以前的工作K+电流将延长， 进一步探讨第二信使的性质和可能的 由毒蕈碱激动剂诱导的钾电流， 识别钾电流的类型， 人心肌的哺乳动物模型：兔心房。 在这些实验中，通过酶促获得的单细胞 将使用来自牛蛙心房或兔心房的分散体， 全细胞电压钳记录和单通道贴片 将进行钳夹记录。 此外，还将尝试 利用短期培养来“保持”细胞群 技术，使预处理与生化途径 抑制剂可以在工作的某些阶段进行。 实验的成功将进一步产生新的数据。 确定了毒蕈碱激动剂抑制 异丙肾上腺素诱导的电流变化，并提供定量 关于家兔复极的详细信息 中庭 在所有的生理状态和某些病理状态下， 条件肾上腺素能紧张是存在的，可以通过调节 多种机制，包括胆碱能神经的变化 活动 这些结果将是相当大的药理学 和病理生理学的重要性， 控制心律失常。