CARDIAC ELECTROPHYSIOLOGY: EFFECTS OF IONS AND DRUGS

描述：（改编自研究者摘要）虽然急性 心脏膜电流的调节一直是研究的主题， 自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。本申请建议 研究心脏电生理学的变化， 几小时到几天将研究两个主要问题：1） 肾素-血管紧张素系统在建立电生理梯度中的作用 产生正常极性的心室壁特性 T波的变化，以及2）长时间刺激引起的离子通道和泵的变化 长期暴露于α或β肾上腺素能激动剂。申请人将聘请一名 多学科方法，包括1）生物物理（膜片钳），2） 分子生物学（RNA酶保护测定），和3）蛋白质化学 （放射免疫测定和磷酸化抗体）。研究结果应该能提供 正常的心脏电生理学，以及发生的变化， 对血管紧张素II或儿茶酚胺水平升高的反应。为 该提案包括对长期ACE抑制动物的研究，AT 1 受体阻滞、α肾上腺素能阻滞和β肾上腺素能阻滞， 这些研究也应该与在 心脏细胞通过长期暴露于这些常用的心血管 药物治疗

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.