Potassium channels comprise a group of transmembrane proteins in cells that typically allow preferential passage of K+ from the inside of the cell to its external environment. In excitable tissues such as neurons and myocytes, these channels functionally hyperpolarize the cell, serving to retard electrical conduction and excitability. In the heart, K+ channels such as Kv1.5 are of paramount importance in cardiomyocyte repolarization and governing the duration of the action potential. Since cardiac arrhythmias arise from abnormal cardiac excitability, the control of cardiac K+ channel modulation constitutes a promising site of clinical therapeutic intervention. It has been proposed that disruption of the actin cytoskeleton leads to an increased surface activity of cloned Kv1.5 channels in human embryonic kidney (HEK) cells. To investigate this hypothesis and its physiological importance, I propose to investigate cytoskeletal disruption in cardiomyocytes as well as HEK cells, examining its effect on levels of gating current in Kv1.5 and the distributions of a-actinin-2 and Kv1.5. In addition, it has been speculated that repolarizing K+ currents underlie the basis of alterations in cardiac action potential configuration occurring during post-natal development. I further propose to examine the possible postnatal changes in Kv1.5 expression contributing to this developmental dependence.