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 (e.g. hypertension, atherosclerosis) in which smooth muscle function may be abnormal. Smooth muscle is characterized by its slow velocity of shortening and economical usage of ATP during force production. These contractile characteristics may reflect the mechanical properties of the basic force generating element, the crossbridge, as well as the kinetics of its cycle. Interpretation of studies in whole tissue, designed to characterize these crossbridge properties, are complicated by the heterogeneous response of a large population of cells that are embedded in a dense connective tissue matrix. To avoid the complexities of multicellular preparations, crossbridge properties will be studied directly, using state of the art techniques to measure mechanical responses from a single smooth muscle cell, isolated from the stomach of the toad, Bufo marinus. Crossbridges are arranged into contractile units within the cell. Contractile unit length will be determined by studying the length dependence of force production. Tension transients in response to small rapd length changes will be used to define the crossbridge elastic properties and rate constants for transitions between steps in the crossbridge cycle. The relationship between force and velocity will be obtained for the first time in single smooth muscle cells. The tension transient and force velocity data will then be used to construct a thermodynamic model of the crossbridge cycle in smooth muscle. The model will predict how the crossbridge cycle time and distribution of crossbridge states relate to smooth muscles slow, economical contraction. The proposed studies will be the first to correlate smooth muscles' contractile capabilities to crossbridge properties.
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