Sodium Channel Isoform Expression in the Retina

State University New York Stony Brook, Stony Brook NY

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Abstract

[unreadable] DESCRIPTION (provided by applicant): 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 [unreadable] [unreadable]