Propagation of electrical signals with high speed and reliability in nerve fibers depends on a complex interaction between neurons and their associated myelinating glial cells. As a result of this interaction ion channels are clustered at specific sites along the axon. This system is studied in both development and disease. At birth axons have little myelin, but by the end of the first postnatal week both glial ensheathment and ion channel clustering are at an advanced state. In multiple sclerosis myelin is damaged, and ion channel distributions are disrupted. The immune mechanisms responsible for this pathology are not known. This laboratory studies the molecular mechanisms responsible for these phenomena using electrophysiology, immunocytochemistry, molecular biology, and transgenic manipulations.
During myelination glial cells have a profound influence on the axonal ion channel distribution. In the peripheral nervous system Schwann cells bind to axons during both development and remyelination. Sodium channels, responsible for the upstroke of the action potential, cluster in the axon membrane adjacent to the tips of Schwann cell processes that are extended during early stages of ensheathment. As Schwann cells grow longitudinally, these channels appear to move with them, ultimately fusing with a neighboring cluster to form a node of Ranvier. Voltage-dependent potassium channels have a reciprocal relationship with sodium channels, and are located primarily in clusters several micrometers on either side of the node. New studies are focused on the central nervous system and combine immunocytochemistry with electrophysiology to determine the distribution and role of ion channels during development of the optic nerve. We seek to determine the cellular and molecular events responsible for ion channel localization and stabilization in the neuronal membrane.
- Single amino acid deletion in transmembrane segment D4S6 of sodium channel Scn8a (Nav1.6) in a mouse mutant with a chronic movement disorder.Neurobiol Dis. 89, 36-45. (2016 Jan 22).
- Th Cell Diversity in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis.J Immunol. 195, 2552-9. (2015 Sep 15).
- DLK-dependent signaling is important for somal but not axonal degeneration of retinal ganglion cells following axonal injury.Neurobiol Dis. 69, 108-16. (2014 Sep 01).