Thesis (Ph. D. in Health Sciences and Technology)--Harvard-MIT Program in Health Sciences and Technology, 2012. / Cataloged from PDF version of thesis. In title on title page, double underscored "v̳" appears as subscript. / Includes bibliographical references (p. 73-83). / Voltage-gated sodium (Nav) channels are diverse, comprising nine known mammalian subunits, which are classified pharmacologically into tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-insensitive (TTX-1) categories. The pattern of Nav channel expression shapes response properties of neurons, while changes in these expression patterns are related to many pathological conditions. Previous RT-PCR results indicated the expression of a variety of Nav channel subunits in the vestibular ganglion, the sensory ganglion that conveys information about motion and orientation. The expressed subunits included several TTX-1 subunits with unique biophysical properties that have been extensively characterized in somatosensory neurons and the heart, but never reported in published electrophysiological studies of the vestibular ganglion. Using whole-cell patch clamp, we show the presence of two types of TTX-l Nav currents in acutely dissociated rat vestibular ganglion neurons (VGNs) from the first postnatal week: a fast and negatively-inactivating current (midpoint of inactivation: ~-100 mV) that resembled current previously described for the Nav1.5 subunit, and a slower current with a depolarized voltage range of inactivation (midpoint ~-30 mV) which had properties consistent with Nav1.8 channels. All neurons also expressed TTX-S Nav currents with similar properties to those previously described in VGN (midpoint of inactivation: ~-75 mV). The Nav1.5-like current contributed about 10% of the total Nav current, was expressed in most VGNs on the first postnatal day (P1), and gradually decreased in prevalence throughout the first week. The Nav1.8-like current was present in ~25% of cells and was correlated with broader action potentials, higher voltage thresholds, and minimal spike height accommodation. We confirmed the expression of Nav1.8 using a reporter mouse in which fluorescence is restricted to Nav1.8- expressing cells; intense fluorescent signal was seen in many VGN cell bodies and peripheral processes. These results suggest that Nav1.8 may be expressed in non-somatosensory peripheral neurons. Nav channel expression in immature VGNs may contribute to development, while differential expression in adulthood may underlie diversity of mature response properties. / by Xiao-Ping Liu. / Ph.D.in Health Sciences and Technology
| Identifer | oai:union.ndltd.org:MIT/oai:dspace.mit.edu:1721.1/78153 |
| Date | January 2012 |
| Creators | Liu, Xiao-Ping, Ph. D. Massachusetts Institute of Technology |
| Contributors | Ruth Anne Eatock and M. Charles Liberman., Harvard--MIT Program in Health Sciences and Technology., Harvard--MIT Program in Health Sciences and Technology. |
| Publisher | Massachusetts Institute of Technology |
| Source Sets | M.I.T. Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 83 p., application/pdf |
| Rights | M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission., http://dspace.mit.edu/handle/1721.1/7582 |
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