This research project is an experimental study that seeks to understand the role of cation-chloride co-transporters in information processing in the mammalian retina. In the retina and elsewhere in the central nervous system, two types of chloride co-transporters, the Na-K-Cl and K-Cl co-transporters, have been identified. These chloride co-transporters regulate the intracellular chloride concentration such that the K-Cl co-transporter extrudes chloride from neurons, whereas the Na-K-Cl co-transporter transports chloride into cells. Thus, the neurotransmitter GABA hyperpolarizes neurons when the chloride equilibrium potential is less than the resting membrane potential due to the action of the K-Cl co-transporter. In contrast, GABA depolarizes neurons when the chloride equilibrium potential is greater than the resting membrane potential due to the action of the Na-K-Cl co-transporter. Thus, depending on the type of chloride co-transporter expressed by a retinal neuron, GABA will either hyperpolarize or depolarize the cell.We will therefore determine the roles of chloride co-transporters in the retina by using a combination of electrophysiological, neurochemical and anatomical techniques. A rabbit eyecup preparation will be used to study the roles of chloride co-transporters in directional selectivity and in synaptic transmission from horizontal cells to bipolar cells. Specifically, we will determine whether an asymmetric distribution of the Na-K-Cl and K-Cl co-transporters on starburst amacrine cells mediates the null direction inhibition exhibited by rabbit ON-OFF directionally-selective ganglion cells. We will also determine whether horizontal cells contribute to the receptive field surround of ON-center bipolar cells (and ON-center ganglion cells) in part by a direct, GABA-mediated synaptic connection that is Na-K-Cl co-transporter-dependent and sign conserving. Finally, we will determine whether and how the development of chloride co-transporter function affects these retinal phenomena.Increased knowledge of chloride co-transporter function in the adult and developing retina will aid in the understanding of human retinal processes and dysfunction, as well as provide the basis for drug therapy for retinal disorders.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY014235-05
Application #
6936508
Study Section
Special Emphasis Panel (ZRG1-SSS-P (01))
Program Officer
Hunter, Chyren
Project Start
2002-09-01
Project End
2007-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
5
Fiscal Year
2005
Total Cost
$299,000
Indirect Cost
Name
Ohio State University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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Dmitriev, Andrey V; Mangel, Stuart C (2004) Retinal pH reflects retinal energy metabolism in the day and night. J Neurophysiol 91:2404-12
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Ribelayga, Christophe; Mangel, Stuart C (2003) Absence of circadian clock regulation of horizontal cell gap junctional coupling reveals two dopamine systems in the goldfish retina. J Comp Neurol 467:243-53