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

电压依赖性Ca2+通道是一种多亚基跨膜蛋白，在多种细胞功能的调节中起关键作用。本研究的长期目标是了解心血管系统中离子通道的生理调节。确定心脏l型Ca2+通道交感调节的机制是实现这一目标的关键一步。具体目标是：(1)建立一个有用的表达系统，其中可以推断支配AR/ l型Ca2+通道相互作用的分子事件；(2)明确-肾上腺素能亚型（1AR和2AR）对心脏l型Ca2+通道调节的相对贡献。受体亚型特异性调节（直接和间接反应）将在转染细胞中进行比较；(3)在分子水平上研究AR中对与Ca2+通道的亚型特异性相互作用至关重要的区域。本研究的长期目标是了解心血管系统中离子通道的生理调节。本研究将利用克隆不同的β -肾上腺素能受体（AR）亚型和心脏Ca2+通道的优势，在分子水平上直接研究AR对Ca2+通道的调控机制。本研究结果将为进一步深入研究离子通道的生理调控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. ***