TRANSMITTER MODULATION OF REPOLARIZATION IN HEART

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 在触发和控制复极以及在 心脏对各种自主神经递质的反应和 其他药理药剂。尽管如此，量化的 关于号码、时间和时间的信息 哺乳动物心脏K+电流的大小(S)是不完整的。在这 提议，之前关于K+电流的工作将延长， 进一步探索宇宙的本质和可能的第二使者 M受体激动剂诱导的钾电流，以及 确定钾电流的类型存在于 人心肌哺乳动物模型：兔心房。 在这些实验中，通过酶处理获得的单个细胞 将使用牛蛙中庭或兔中庭的分散剂 全电池电压钳记录和单通道贴片 将制作夹具录音。此外，还将尝试 利用短期孵化来“容纳”细胞群体 用生化途径进行前处理的技术 抑制剂可以在工作的某些阶段进行。 拟议实验的成功将进一步产生新的数据 确定毒鼠碱激动剂抑制的机制 异丙肾上腺素诱发的电流变化，并提供定量 关于兔的复极细节的信息 中庭。在所有生理状态和某些病理状态下 存在肾上腺素能张力的条件，并可通过 多种机制，包括胆碱能神经的变化 活动。这些结果将具有相当大的药理学意义。 和病理生理学上的重要性 心律失常的控制。

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.