Hemi-gap-junction (HGJ) channels composed of connexin (Cx) proteins are proposed as the key component to mediate the negative feedback pathway from horizontal cells (HCs) to photoreceptors in the outer retina. The goal of the research undertaken in this dissertation was to test whether HGJ channels in retinal HCs could serve their proposed roles in the negative feedback pathway. First, the biophysical properties of HGJ channels and their modulation by the neuromodulator zinc using electrophysiological methods were characterized. Both outward and inward hemichannel currents were elicited in cultured solitary zebrafish retinal HCs. In particular, inward hemichannel currents elicited at negative potentials persisted under physiological conditions and satisfy the requirement of ephaptic communication in the feedback pathway. In addition, to uncover the molecular basis of the HGJ currents, the function and properties of various Cx proteins were studied using morpholino-based gene knockdown and a cx55.5 mutant zebrafish. The data suggest that inward hemichannel currents are solely dependent on the expression of Cx55.5, while outward hemichannel currents are dependent by both Cx55.5 and Cx52.6. In summary, this study expands our understanding in the properties and function of HGJ channels and the mechanisms underlying neuronal network adaptation in retinal circuitry.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-11302009-182305 |
| Date | 02 December 2009 |
| Creators | Sun, Ziyi |
| Contributors | Joshua T. Gamse, David J. Calkins, Douglas G. McMahon, Terry L. Page, Laurence J. Zwiebel |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu//available/etd-11302009-182305/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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