This proposal will investigate the role of voltage-dependent sodium channel (Nav) isoforms in retinal visual processing. Nav's play the critical role of supporting the rising phase of the action potential, and despite the strong similarity among the Nav isoforms, misexpression of specific isoforms has been implicated in such disorders as epilepsy, long QT syndrome, multiple sclerosis, and a variety of movement disorders. The proposed studies will examine the Nav expression pattern in the developing retina, and investigate how the isotype-specific distribution of these channels within a neuron influences its cellular properties and responsibilities within the retinal mosaic. The proposed research will build on previous work in this lab showing that specific Nav isoforms are targeted to morphologically and functionally distinct compartments within retinal ganglion cells, and their expression is developmentally regulated. Combinations of tract-tracing and immunohistochemistry will be used to see which Navs localize to retinal ganglion cell terminal endings over development, and to determine which cell types express Navs in the inner retina, lmmunohistochemistry and intracellular recordings will then be used to look at the role of Nav1.6 at the initial segment of retinal ganglion cell axons by examining differences in ganglion cell physiology and Nav distribution in med mice who lack Navl.6. The goal is to not only contribute to our understanding of how visual signals are processed, but also to shed light on the mechanisms behind disease-causing channelopathies of the muscle, heart, and nervous system ? ?
| Van Wart, Audra; Trimmer, James S; Matthews, Gary (2007) Polarized distribution of ion channels within microdomains of the axon initial segment. J Comp Neurol 500:339-52 |
| Van Wart, Audra; Matthews, Gary (2006) Impaired firing and cell-specific compensation in neurons lacking nav1.6 sodium channels. J Neurosci 26:7172-80 |
| Van Wart, Audra; Matthews, Gary (2006) Expression of sodium channels Nav1.2 and Nav1.6 during postnatal development of the retina. Neurosci Lett 403:315-7 |
| Van Wart, Audra; Boiko, Tatiana; Trimmer, James S et al. (2005) Novel clustering of sodium channel Na(v)1.1 with ankyrin-G and neurofascin at discrete sites in the inner plexiform layer of the retina. Mol Cell Neurosci 28:661-73 |
