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. ***
