Investigation of hemi-gap-junction channels in retinal horizontal cells

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.