ELECTROPHYSIOLOGY OF HUMAN REPRODUCTIVE SMOOTH MUSCLE

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Preterm labor and deliver is a problem of profound national importance. As clinicians, we are hindered in the prevention and treatment of preterm labor by a lack of understanding of the microscopic details of the initiation of labor, maintenance of labor, and possible points of intervention. In order to define the details of the electrophysiology of human reproductive smooth muscle and the mechanisms of drug action, we propose here to perform microelectrode studies on isolated pregnant human uterine myocytes and their cultures. A protocol for the enzymatic dispersion and isolation of individual myocytes from pregnant human myometrium will be determined. Cells cultured in the presence of pregnant human serum will also be studied to determine the effects of the hormones of pregnancy on electrophysiologic parameters. Over the past ten years the technique of patch clamping has been developed and exploited to study many types of cells, including neurologic, cardiac, and smooth muscle. The patch clamp is a specialized technique that allows various types of measurements to be performed. Using the "whole cell" voltage clamp, the contributions of specific ions to the excitability of the cell will be determined. A powerful aspect of the patch clamp technique is in the ability to study small patches of membrane. This technique will allow observation of ion specific channels, and the effects of drugs on the channels.