MANIPULATION OF CALCIUM CHANNELS TO REGULATE AFTER-DEPOLARIZATION EVENTS IN CARDIAC MYOCYTES

摘要

A novel mechanism by which after-depolarization occurs in cardiac myocytes has been discovered, involving calcium influx through the arachidonate-regulated calcium channel (ARCC) and the store-operated calcium channel (SOCC). Because after-depolarization of the myocyte is a major cause of cardiac arrhythmia, this discovery provides new approaches for treating and preventing heart disease. By down-regulating the activity of the ARCC or the SOCC, after-depolarization can be decreased and cardiac arrhythmia can be prevented, reduced, or eliminated. This can be accomplished using pharmaceuticals containing inhibitors of the ARCC or the SOCC, or by genetically modifying cells to reduce ARCC or SOCC activity. In addition, assays are disclosed using the ARCC or SOCC to discover potential anti-arrhythmic agents. Cellular and animal models of arrhythmia are disclosed in which the activity of the ARCC or SOCC is increased to promote after-depolarization and induce arrhythmia.