PHARMACOLOGY OF NA+-, CA++- AND K+-ANTAGONISTS IN CELLS

NA -、CA - 和 K - 拮抗剂在细胞中的药理学

• 批准号: 3341195
• 负责人: Joseph R Hume
• 金额: $ 6.82万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3341195
• 关键词: action potentials; antiarrhythmic agent; atrium; calcium channel blockers; cations; drug metabolism; heart cell; heart pharmacology; ion transport; lidocaine; membrane permeability; quinidine; tetrodotoxin

Funds are requested to continue support of a study of the specificity and mechanism of action of a variety of Na+, Ca++ and K+ -antagonists in enzymatically dispersed single myocytes from frog and guinea-pig hearts. In comparison to multicellular cardiac preparations, isolated single cells offer a number of important advantages for quantitative voltage-clamp and pharmacological studies: (i) the ability to study possible mechanisms of pharmacological modulation of ion channel function both at the level of whole-cell ionic currents as well as single channel currents, and (ii) the ability to carefully assess the specificity of pharmacological agents on each component of ionic current under conditions in which contamination by other currents is minimal. Considerable recent progress has been made in understanding the interactions of several organic Ca++ channel antagonists with Ca++ and K+ channels in single frog atrial myocytes. We propose to continue these experiments in isolated single guinea-pig myocytes to include an analysis of the mechanism of action and specificity of several Na+ and K+ channel antagonists. Since many of the compounds to be studied are important therapeutic agents used clinically to treat a variety of cardiovascular conditions, the proposed experiments will provide new information with regard to the cellular actions of these compounds. This information will contribute to a better understanding of cardiac arrhythmias in general and may lead to the development of newer and more effective antiarrhythmic agents.

要求提供资金，以继续支持研究 各种Na+、Ca++和K+ -拮抗剂的作用机制 从青蛙和豚鼠心脏酶分散的单个肌细胞。 与多细胞心脏制备物相比，分离的单细胞 为定量电压钳提供了许多重要的优点， 药理学研究：（一）研究可能的机制的能力 离子通道功能的药理学调节， 全细胞离子电流以及单通道电流，和（ii） 能够仔细评估药理学试剂对 离子电流的每一个组成部分的条件下，其中污染 其他电流是最小的。 最近在了解 几种有机Ca ~（++）通道拮抗剂与Ca ~（++）和K ~（++）的相互作用 单个青蛙心房肌细胞中的通道。 我们建议继续这些 在分离的单个豚鼠肌细胞中进行的实验， 几种Na+和K+通道的作用机制和特异性 对手。 由于许多待研究的化合物是重要的治疗剂 临床上用于治疗各种心血管疾病， 拟议的实验将提供关于 这些化合物的细胞作用。 这些信息将有助于 更好地了解心律失常的一般，并可能导致 开发更新和更有效的抗肿瘤药物。