Ion channels are critical for normal electrical activity in cardiac and vascular smooth muscle, while even mild dysfunction can cause life-threatening cardiac arrhythmias in humans. The principal goal of our research is to investigate the signaling processes and proteins that modulate the activity of cardiovascular ion channels. Circulating hormones that activate intracellular signaling cascades, and ultimately protein kinases, can rapidly regulate ion channel function. Our recent work demonstrates that protein kinases can also modify intracellular trafficking of cardiac sodium channels to alter expression at the cell surface. Given the critical role of these channels in electrical impulse conduction, we are actively investigating the molecular features of this process. We have also chosen to study a potassium channel signaling complex that underlies an important repolarizing current, IKur. Because IKur is atrial-specific in humans, it represents an attractive target for pharmacologic therapy of cardiac arrhythmias, and improved understanding of its molecular components would permit optimal drug design. Another area of interest is the electrical remodeling that occurs with atrial fibrillation, a common cardiac arrhythmia that is a major cause of stroke and death in the US. The remodeling process causes the arrhythmia to perpetuate itself, rendering it refractory to treatment. An in vitro model of atrial fibrillation has been created to investigate basic mechanisms of development and associated changes in gene expression. These studies should improve our understanding of the molecular basis of ionic currents in the cardiovascular system and contribute to the development of new therapeutic approaches in treating cardiac arrhythmias.