ALPHA ADRENERGIC REGULATION OF CARDIAC ION CHANNELS

心脏离子通道的 ALPHA 肾上腺素调节

• 批准号: 6168899
• 负责人: ROBERT D HARVEY
• 金额: $ 21.74万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6168899
• 关键词: alpha adrenergic receptor; beta adrenergic receptor; biological signal transduction; calcium channel; cardiac myocytes; chloride channels; cyclic AMP; electrophysiology; guinea pigs; membrane channels; pertussis toxin; phospholipase A2; phospholipase C; potassium channel; protein tyrosine kinase; receptor sensitivity

DESCRIPTION: Preliminary data from the PI's laboratory has demonstrated that activation of alpha-1 adrenergic receptors inhibits beta-adrenergic induced stimulation of cardiac ion channels, particularly the C1 channel. The project proposed to extend these observations to other ion channels and to delineate the mechanisms involved. The proposal has 3 specific aims: (1) The PI will determine if alpha-1 adrenergic activation inhibits beta-stimulation in a similar fashion for C1 currents, L-type Ca currents and delayed rectified K currents. (2) It will be determined if alpha-1 adrenergic stimulation exerts its effects by changing cAMP production or degradation or by interactions involving the beta receptor itself, such as facilitating receptor desensitizations (3) The pathway involved in these effects will be delineated by identifying the subtype of alpha-adrenergic receptor involved, assessing pertussis toxin sensitivity and investigating the possible roles of phospholipase C, phospholipase A2 and tyrosine kinases.

描述：PI 实验室的初步数据表明 α-1 肾上腺素能受体的激活抑制 β-肾上腺素能受体 诱导刺激心脏离子通道，特别是 C1 通道。 该项目建议将这些观察扩展到其他离子通道 并描述所涉及的机制。该提案有3项具体内容 目标：(1) PI 将确定 alpha-1 肾上腺素能激活是否会抑制 以类似方式对 C1 电流、L 型 Ca 电流进行 β 刺激 和延迟整流 K 电流。 (2) 判断是否为alpha-1 肾上腺素能刺激通过改变 cAMP 的产生或 降解或涉及β受体本身的相互作用，例如 促进受体脱敏 (3) 参与这些的途径 通过识别α-肾上腺素能的亚型来描述效果 涉及受体，评估百日咳毒素敏感性并调查 磷脂酶 C、磷脂酶 A2 和酪氨酸的可能作用 激酶。

项目成果

Tyrosine phosphatase inhibitors selectively antagonize beta-adrenergic receptor-dependent regulation of cardiac ion channels.

酪氨酸磷酸酶抑制剂选择性拮抗心脏离子通道的β-肾上腺素受体依赖性调节。

• DOI: 10.1124/mol.58.6.1213
• 发表时间: 2000
• 期刊: Molecular pharmacology
• 影响因子: 3.6
• 作者: Sims,C;Chiu,J;Harvey,RD
• 通讯作者: Harvey,RD

Role of tyrosine kinase activity in alpha-adrenergic inhibition of the beta-adrenergically regulated L-type Ca(2+) current in guinea-pig ventricular myocytes.

酪氨酸激酶活性在α-肾上腺素能抑制豚鼠心室肌​​细胞中β-肾上腺素调节的L-型Ca(2)电流中的作用。

• DOI: 10.1111/j.1469-7793.2001.00779.x
• 发表时间: 2001
• 期刊: The Journal of physiology
• 作者: Belevych,AE;Nulton-Persson,A;Sims,C;Harvey,RD
• 通讯作者: Harvey,RD