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TRANSMITTER MODULATION OF REPOLARIZATION IN HEART

心脏复极的发射机调制

基本信息

批准号：
3472238
负责人：
ERWIN F SHIBATA
金额：
$ 6.38万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-07-01 至 1994-06-30
项目状态：
已结题

项目摘要

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.

心脏中与时间和电压相关的 K+ 电流为对起搏器的发展至关重要潜力，在触发和控制复极以及心脏对各种自主发射器的反应和其他药理制剂。尽管如此，定量有关数量、时间进程和哺乳动物心脏中 K+ 电流的大小并不完整。在这个提议，之前关于 K+ 电流的工作将被扩展，通过进一步探索自然和可能的第二信使毒蕈碱激动剂诱导的钾电流，以及识别钾电流的类型人类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液，并且全细胞电压钳记录和单通道贴片将进行钳位录音。此外，还将尝试通过短期孵育来“保存”细胞群技术，以便通过生化途径进行预处理抑制剂可以在某些阶段进行工作。拟议实验的成功将进一步产生新数据确定毒蕈碱激动剂抑制的机制异丙肾上腺素引起的电流变化，并提供定量有关兔子复极细节的信息中庭。在所有生理状态和某些病理状态下条件肾上腺素能张力存在并且可以通过调节多种机制，包括胆碱能神经的变化活动。这些结果将具有重要的药理学意义和病理生理学的重要性在理解和控制心律失常。