ALPHA ADRENERGIC REGULATION OF CARDIAC ION CHANNELS

描述：PI实验室的初步数据表明， 激活α-1肾上腺素能受体抑制β-肾上腺素能 诱导心脏离子通道，特别是C1通道的刺激。 该项目建议将这些观察扩展到其他离子通道 并描述其机制。该提案有三个具体 目的：（1）PI将确定α-1肾上腺素能激活是否抑制 以类似的方式刺激C1电流、L型Ca电流 和延迟整流的K电流。(2)将确定阿尔法-1 肾上腺素能刺激通过改变cAMP的产生或 降解或通过涉及β受体本身的相互作用，如 促进受体脱敏（3）参与这些过程的途径 将通过鉴定α-肾上腺素能受体的亚型来描述其作用。 受体参与，评估百日咳毒素敏感性和研究 磷脂酶C、磷脂酶A2和酪氨酸的可能作用 激酶。

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.