Description:

The Department of Pharmacology is pleased to welcome Dr. Miriam Meisler, Ph.D. as our Third Annual Julius B. Kahn Lecturer. Dr. Meisler is the Myron Levine Distinguished University Professor in the Departments of Human Genetics and Neurology at the University of Michigan.

The following, is an overview of this seminar, as described by Dr. Meisler:

Voltage-gated sodium channels are among the most highly conserved proteins in the human genome. These large transmembrane channels have evolved to generate brief pulses of sodium ion entry into excitable cells. In neurons these pulses are responsible for initiation and propagation of action potentials. Mutations that change the amino acid sequence of these highly evolved molecular machines are poorly tolerated, and lead to inherited and sporadic neurological disorders. The sodium channel Nav1.6 is encoded by the gene SCN8A, and is broadly expressed in the CNS and PNS. Several hundred mutations of SCN8A have been identified in patients with seizure disorders, impaired movement, and intellectual disability. We are using mouse models expressing patient mutations to investigate their effects on neuronal function as well as responses to therapeutic interventions. We will describe the effects of epileptogenic mutations on Nav1.6 function in transfected cells and the altered properties of neurons and cardiac myocytes in Scn8a mutant mice.