Stable Expression and Beta-adrenergic Receptor Subtype- Specific Regulation of the Cardiac L-type Ca2+ Channel

9509164 Yatani是一种电压依赖性钙离子通道，是一种多亚单位跨膜蛋白，在多种细胞功能的调节中起着关键作用。本研究的长期目标是了解心血管系统离子通道的生理调节。确定交感神经调节心脏L钙通道的机制是实现这一目标的关键一步。具体的目标是：(1)建立一个有用的表达系统，在其中可以推断控制AR/L型钙通道相互作用的分子事件；(2)确定肾上腺素能亚型(1AR和2AR)在心脏L型钙通道调节中的相对贡献。将在转基因细胞中比较受体亚型特异性调节(直接和间接反应)；以及(3)在分子水平上研究AR的区域，这些区域对于亚型特异性与钙通道的相互作用至关重要。本研究的长期目标是了解心血管系统离子通道的生理调节。这项研究将利用不同的β-肾上腺素能受体(AR)亚型和心脏钙通道的克隆，在分子水平上直接研究AR对钙通道的调节机制。这项研究的结果将为更深入地研究离子通道的生理调节提供初步的数据基础。***

9509164 Yatani The voltage-dependent Ca2+ channel is a multi-subunit membrane- spanning protein that plays a critical role in the regulation of a variety of cell functions. The long-term goal of this research is to understand the physiological regulation of ion channels in the cardiovascular system. The identification of the mechanism underlying sympathetic modulation of the cardiac L-type Ca2+ channel is a key step in achieving this goal. Specific aims are: (1) To establish an useful expression system in which the molecular events which govern AR/L-type Ca2+ channel interactions can be deducted; (2) To define the relative contribution of -adrenergic subtypes ( 1AR and 2AR) to cardiac L-type Ca2+ channel regulation. The receptor subtype-specific regulation (both direct and indirect responses) will be compared in transfected cells; and (3) To investigate, at the molecular level, the regions of the AR which are critical for subtype-specific interactions with the Ca2+ channel. %%% The long-term goal of this research is to understand the physiological regulation of ion channels in the cardiovascular system. The research will take advantage of the cloning of the distinct beta-adrenergic receptor ( AR) subtypes and of the cardiac Ca2+ channel, and examine directly the regulatory mechanisms of AR on the Ca2+ channel at the molecular level. The results obtained from this research will serve as an initial data base for a more thorough study of the physiological regulation of ion channels. ***