Small reductions in extracellular chloride suppress light-evoked currents in second-order retinal neurons. Thus, physiological regulation of chloride in and around photoreceptors may act in concert with photoreceptor membrane voltage to control transmitter release at this critical first synapse in vision. Regulation of photoreceptor neurotransmission by chloride could affect vision in many ways. For example, changes in chloride levels during sustained illumination might play a role in post-receptoral adaption; chloride fluxes during illumination of the cone receptive field surround could adjust the strength of surround antagonism; and activity-dependent changes in chloride should alter the balance between ON and OFF light responses (which could account for the enhanced sensitivity of ON retinal ganglion cells to ischemia). To assess possible functions of chloride regulation, it is essential to understand the mechanism(s) responsible for the suppression of transmitter release from photoreceptors induced by reductions in extracellular chloride. Besides suppressing light-evoked currents in horizontal and bipolar cells, reducing chloride suppresses the dihydropyridine-sensitive calcium current in photoreceptors. Suppression of this current by dihydropyridine antagonists reduces light responses in second-order retinal neurons. Therefore, it is hypothesized that the suppression of light-evoked currents in second order retinal neurons may arise as a consequence of the suppression of photoreceptor calcium currents induced by reductions in chloride. The two major aims of this proposal are to test this hypothesis further and to analyze the mechanism(s) by which chloride may influence calcium channel function. Whole cell and single channel patch clamp recordings will be used to study the chloride sensitivity of photoreceptor calcium currents, as well as currents evoked by light and spontaneous quantal release in horizontal and bipolar cells of the amphibian retina. These experiments should provide an understanding of the photoreceptor mechanisms responsible for chloride regulation and provide a sound basis for future studies into possible functions of this newly identified regulatory mechanism.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29EY010542-03
Application #
2711106
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1996-06-01
Project End
2001-05-31
Budget Start
1998-06-01
Budget End
1999-05-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Nebraska Medical Center
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
City
Omaha
State
NE
Country
United States
Zip Code
68198
Grassmeyer, Justin J; Thoreson, Wallace B (2017) Synaptic Ribbon Active Zones in Cone Photoreceptors Operate Independently from One Another. Front Cell Neurosci 11:198
Van Hook, Matthew J; Babai, Norbert; Zurawski, Zack et al. (2017) A Presynaptic Group III mGluR Recruits G??/SNARE Interactions to Inhibit Synaptic Transmission by Cone Photoreceptors in the Vertebrate Retina. J Neurosci 37:4618-4634
Datta, Proleta; Gilliam, Jared; Thoreson, Wallace B et al. (2017) Two Pools of Vesicles Associated with Synaptic Ribbons Are Molecularly Prepared for Release. Biophys J 113:2281-2298
Cork, Karlene M; Van Hook, Matthew J; Thoreson, Wallace B (2016) Mechanisms, pools, and sites of spontaneous vesicle release at synapses of rod and cone photoreceptors. Eur J Neurosci 44:2015-27
Plog, Stephanie; Klymiuk, Nikolai; Binder, Stefanie et al. (2015) Naturally Occurring Deletion Mutants of the Pig-Specific, Intestinal Crypt Epithelial Cell Protein CLCA4b without Apparent Phenotype. PLoS One 10:e0140050
Thoreson, Wallace B (2015) Horizontal slices of mouse retina expose horizontal cells and their properties (Commentary on Feigenspan & Babai). Eur J Neurosci 42:2613-4
Van Hook, Matthew J; Parmelee, Caitlyn M; Chen, Minghui et al. (2014) Calmodulin enhances ribbon replenishment and shapes filtering of synaptic transmission by cone photoreceptors. J Gen Physiol 144:357-78
Bennett, Lea D; Hopiavuori, Blake R; Brush, Richard S et al. (2014) Examination of VLC-PUFA-deficient photoreceptor terminals. Invest Ophthalmol Vis Sci 55:4063-72
Cork, Karlene M; Thoreson, Wallace B (2014) Rapid kinetics of endocytosis at rod photoreceptor synapses depends upon endocytic load and calcium. Vis Neurosci 31:227-35
Sim, S L; Szalewski, R J; Johnson, L J et al. (2014) Simultaneous recording of mouse retinal ganglion cells during epiretinal or subretinal stimulation. Vision Res 101:41-50

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