CARDIAC ELECTROPHYSIOLOGY: EFFECTS OF IONS AND DRUGS

描述：(改编自《调查者摘要》) 心肌细胞膜电流的调节一直是人们研究的热点 膜片钳技术问世以来的长期研究 调制受到的关注要少得多。此应用程序建议 研究心脏电生理学在一段时间内发生的变化 从几小时到几天。将调查两个主要问题：1) 肾素-血管紧张素系统在建立电生理梯度中的作用 产生正常极性的跨室壁的特性 2)Long引起的离子通道和泵的改变 长期接触α或β肾上腺素能激动剂。申请人将雇用一名 多学科方法，包括1)生物物理学(膜片钳)，2) 分子生物学(核糖核酸酶保护分析)和3)蛋白质化学 (放射免疫分析和磷抗体)。结果应该会提供洞察力 转化为正常的心脏电生理学，以及发生在 对血管紧张素II或儿茶酚胺水平升高的反应。作为 该提案包括对维持慢性ACE抑制的动物的研究，AT1 受体阻断，α-肾上腺素能阻断，β-肾上腺素能阻断， 这些研究也应该与引起的电学变化有关 心脏细胞长期暴露于这些常用的心血管系统 药物。

DESCRIPTION: (Adapted from the Investigator's Abstract) Although acute modulation of cardiac membrane currents has been the subject of intensive investigation since the advent of the patch clamp technique, long-term modulation has received much less attention. This application proposes to investigate changes in cardiac electrophysiology that occur over a period of hours to days. Two major questions will be investigated: 1) the role played by the renin-angiotensin system in setting up the gradient in electrical properties across the ventricular wall which gives rise to the normal polarity of the T-wave, and 2) the changes induced in ion channels and pumps by long term exposure to alpha or beta adrenergic agonists. The applicant will employ a multidisciplinary approach including 1) biophysical (patch clamping), 2) molecular biology (RNase protection assays), and 3) protein chemistry (radioimmunoassays and phosphoantibodies). The results should provide insight into normal cardiac electrophysiology, as well as the changes that occur in response to elevated levels of angiotensin II or catecholamines. As the proposal includes studies of animals maintained on chronic ACE inhibition, AT1 receptor blockade, alpha adrenergic blockade, and beta adrenergic blockade, these studies should also be relevant to the electrical changes induced in cardiac cells by chronic exposure to these commonly used cardiovascular medications.