Date of Award
Summer 1996
Document Type
Dissertation - Restricted
Degree Name
Doctor of Philosophy (PhD)
Department
Biological Sciences
First Advisor
Eddinger, Thomas
Second Advisor
Fitts, Robert
Third Advisor
Piacsek, Bela
Abstract
The goal of this project was to extend our knowledge of the regulation and function of the smooth muscle myosin isoforms. Smooth muscle cells are widely distributed throughout the vertebrate body. The circulatory, digestive, reproductive, respiratory, urinary, and visual systems all include smooth muscle components. Smooth muscle cells express multiple isoforms of myosin including smooth and nonmuscle heavy and light chains. The relative levels of these various myosin isoforms depends upon the species, the tissue, the age, and the health of the source. Thus, it appears that the myosin molecule is regulated in a complex manner. Some of these changes in expression can be mimicked by experimental perturbations, such as urethral obstruction, balloon catheterization, and cell culture. However, many questions regarding the function of these many myosin isoforms need to be addressed directly. This project focused on the smooth muscle myosin heavy chain (SM-MHC) 3' tail isoforms, SM1 and SM2. Previous work at the tissue and molecular levels has shed some light on the function of these isoforms, however some results appear contradictory. At the tissue level, the averaging effect of studying a heterogeneous population may obscure the relative influence of the SM-MHC isoforms. Studies at the molecular level examine the function of the myosin molecule outside its native environment, the myosin filament. This project has developed a protocol which can bridge the gap between the tissue and molecular studies and allow the assessment of the contractile properties of individual smooth muscle cells (SMCs) with known SM1 and SM2 expression levels...