Robert W. Mercer, PhD
Professor of Cell Biology and Physiology
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Washington University in St. Louis (WU)
Mutations in the KCNJ10 gene are responsible for a diverse range of abnormalities that includes epilepsy, deafness, ataxia, mental retardation and electrolyte imbalance. This syndrome, termed SeSAME (seizures, sensorineural deafness, ataxia, mental retardation and electrolyte abnormalities) is a result of the loss in function of the Kir4.1 potassium channel. While some of the mutations compromise channel activity, several of the mutations decrease plasma membrane channel expression. However, it remains to be determined if any of the identified SeSAME mutations affect the polarized sorting of the Kir4.1 polypeptide to the basolateral surface of epithelial cells. To better characterize the trafficking of Kir4.1 to the basolateral membrane we are expressing wild-type and mutant Kir4.1 polypeptides in polarized cells. In addition we are determining if expression of wild-type or mutant Kir4.1 polypeptides in cells influences the Na,K-ATPase activity to modify transepithelial potential, resistance, transport or short-circuit currents. These studies will provide important understandings into the physiological consequences of loss of Kir4.1 function and will help explain the abnormalities associated with the disease.