Access Type

Open Access Dissertation

Date of Award

January 2013

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Anatomy and Cell Biology

First Advisor

Zhuo-Hua Pan

Abstract

Retinal bipolar cells, conveying visual information from photoreceptors to ganglion cells, segregate visual information into multiple parallel pathways through their diversified cell types and physiological properties. Voltage-gated Ca2+ channels could be particularly important underlying the diversified physiological properties of different BCs. In this dissertation, I investigated the high-voltage-activated (HVA) calcium current in retinal bipolar cells in mice. In the first part of my dissertation, I characterized multiple bipolar cell-expressing GFP and/or Cre transgenic mouse lines. In the second part of my dissertation, by performing whole-cell patch-clamp recordings, I examined the electrophysiological properties of HVA calcium currents among CBCs and between CBCs and CBCs. In particular, the second part of my study focused on the investigation of electrophysiological, pharmacological, and molecular properties of HVA calcium currents in RBCs. The results of my studies showed that the HVA Ca2+ currents with different electrophysiological properties were observed among CBCs, and between CBCs and RBCs. First, large HVA Ca2+ currents were observed in OFF CBCs but not in ON-CBCs. Second, HVA Ca2+ currents among different bipolar cells were found to show different activation potentials. Furthermore, the HVA Ca2+ currents in RBCs exhibited two components, a sustained and a transient component with the latter activated at more negative potentials. My pharmacological results indicated the sustained and transient HVA Ca2+ currents are originated from L- and P/Q type Ca2+ channels, respectively. Using L-type Ca2+ channel knockout or deficient mouse lines, my results showed that the L-type Ca2+ currents in RBCs are mediated mainly by alpha1C Ca2+ channels with a minor component from alpha1F Ca2+ channels. The studies will advance our understanding of the role of voltage-gated Ca2+ channels in basic visual information processing in the retina as well as Ca2+ signaling and Ca2+ channel deficit-related diseases in the visual system.

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