Summary
- My areas of research interests include cardiac and smooth muscle electrophysiology and pharmacology, and excitation-contraction coupling mechanisms. One of the major contributing causes of death following acute myocardial infarction is the development of electrical disorders of the heart (arrhythmias). Antiarrhythmic drug therapy is used clinically to correct and prevent occurrences of these arrhythmias. A primary research goal of my laboratory is to gain a better understanding of the electrical properties of cardiac muscle at the level of individual cells and how these properties are modified by various pharmacological agents. We are also interested in gaining a better understanding of the electrical activity of individual smooth muscle cells isolated from a variety of blood vessels (including renal and pulmonary arteries). A more complete understanding of the relationship between electrical activity and mechanical tone in these cells could lead to the development of new antihypertensive agents. Individual myocytes can be isolated from the heart or blood vessels by utilizing an enzymatic dispersion method. The application of the patch clamp technique allows ion channels responsible for the action potential and resting membrane potential to be studied quantitatively. It is also possible to combine the patch clamp technique with calcium-sensitive dyes internally perfused to study the relationship between ion channel activity and changes in intracellular calcium concentration in single cells. Using these methods we have recently characterized the properties of a number of different chloride channels in heart and vascular smooth muscle cells, as well as the properties of ion channels in pulmonary arterial smooth muscle cells whose activity is dependent upon oxygen tension. In collaboration with other investigators associated with the Center of Biomedical Research Excellence (COBRE), we have recently cloned several chloride channels from heart and are performing structure-function studies of these proteins and using functional genomic approaches to determine their physiological and possible pathophysiological role in human cardiovascular function and disease, and are actively investigating their the regulation of calcium channels in smooth muscle cells by intracellular cyclic nucleotides and G proteins.
Education
- Ph.D., 1979, UCSF