Pharmacology & Physiology

Research Interests

 

Calcium Regulation in Smooth Muscle Sarcoplasmic Reticulum

Calcium (Ca) ions are the essential stimulus for development of tension and contraction in smooth muscle cells. The most important organelle regulating Ca activity inside the cell is the sarcoplasmic reticulum (SR). The SR membranes are directly accessible to manipulation following chemical skinning, which uses detergents to make the plasma membrane permeable to ions and small molecules. Research in my laboratory uses saponin skinned rat caudal artery and 45 Ca to investigate the mechanism of Ca release by the SR in a smooth muscle resistance vessel. Ca release is mediated by two separate and functionally distinct Ca channels. One, the ryanodine receptor, is regulated by Ca itself, and the other is activated by inositol triphosphate. In smooth muscle cells, progress has been made in cloning channel proteins, but their exact structure and regulation as well as their contribution to clinical vascular disorders have not been elucidated. SR Ca channel are modulated by therapeutic agents and understanding Ca homeostatic mechanisms may lead to improved drug therapy.