Michael E. Fultz

Smooth muscle demonstrates several unique properties that are poorly understood.  These include the ability to generate force with reduced myosin and the ability to maintain tension with low energy expenditure.  We have proposed that remodeling of the cytoskeketon may explain these properties.  Specific chemical inhibition of several cellular kinases including PKC, CAMK II, MLCK, and Rho kinase in freshly isolated rat aortic smooth muscle tissue rings as well as A7r5 smooth muscle cells demonstrate a strong correlation of force development with alpha-actin remodeling in smooth muscle.  These studies have also suggested that alpha- and beta-actin remodeling may be regulated by separate mechanisms.  The major focus in the laboratory is to determine the mechanism(s) that regulates the dramatic remodeling of each component of the cytoskeleton and how these events contribute to force development and tension maintenance in smooth muscle.  To help determine the mechanism of remodeling, we utilize inhibitor peptides, as well as specific kinase inhibitors to selectively block key kinases and regulatory proteins.  We will examine the effects of this inhibition on alpha-actin, beta-actin, myosin, as well as A7r5 cell contraction using various microscopy techniques.  I am also collaborating with Dr. Darrin DeMoss in the development of a low estrogen cell culture environment that will allow for the study of calcium channel antagonists in cultured bone cells.