Christopher N. Johnson, Ph.D. Molecular basis of fast inactivation for the human cardiac sodium channel

The human cardiac sodium channel (NaV1.5) plays a critical role in heart contraction. Perturbation of the channel function can result in arrhythmias and in some cases stroke or death. Previous work has shown channel inactivation utilizes specific elements of the NaV1.5 C-terminus and the ubiquitous calcium sensing protein calmodulin to translate changes in intracellular calcium. Currently there are conflicting views in the literature for how this occurs and the molecular details of these interactions remain largely unknown. Using a compliment of biophsyical techniques with electrophysiology this work is focused on understanding molecular details that are essential for proper NaV1.5 function. These results allow for the design of structure-based mutantions that provide insight into the molecular basis of specific cardiac life threatening arrhythmias.