Smooth muscle contraction is essential to normal function of many organ systems in the body. Therefore, an understanding of its normal contractile process is required before studying disease states such as hypertension in which smooth muscle function may be abnormal. Smooth muscle is characterized by its slow shortening velocity and economical useage of ATP during force production. These contractile properties may reflect both the mechanics of the basic force generating element, the myosin crossbridge, and its cyclic interaction with actin. To characterize crossbridge properties in smooth muscle, stare-of-the-art techniques will be used to measure mechanical responses from a single smooth muscle cell, isolated from the toad stomach. The single cell approach will avoid the heterogeneity of cellular responses that can occur in multicellular tissue preparations. To correlate a smooth muscle cell's contractile capabilities to its crossbridge properties, changes in cell length will be used as a means of probing the crossbridge cycle. In addition to mechanical perturbations, membrane permeabilized cells will provide the opportunity to modify the cell's interior chemical environment. Thus changes in the cell's free intracellular concentrations of specific ions (e.g. MgATP) and the effect these chemical perturbations have upon cell mechanics will help identify the specific steps in the crossbridge cycle. Finally, a mathematical model of the crossbridge cycle in smooth muscle, that incorporates the mechanical data obtained in this proposal, will be used to formulate a view of the crossbridge cycle in smooth muscle to help explain smooth muscle's slow, economical contraction.
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