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Title page for ETD etd-11302009-182305


Type of Document Dissertation
Author Sun, Ziyi
Author's Email Address ziyi.sun@vanderbilt.edu
URN etd-11302009-182305
Title Investigation of hemi-gap-junction channels in retinal horizontal cells
Degree PhD
Department Biological Sciences
Advisory Committee
Advisor Name Title
Terry L. Page Committee Chair
David J. Calkins Committee Member
Douglas G. McMahon Committee Member
Joshua T. Gamse Committee Member
Laurence J. Zwiebel Committee Member
Keywords
  • Hemi-Gap-Junction Channel
  • Retina
  • Horizontal Cell
  • Patch Clamp
  • Morpholino
  • Zebrafish
Date of Defense 2009-08-28
Availability unrestricted
Abstract
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.
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