Antagonists of protein kinase C inhibit rat retinal glutamate transport activity in situ

Bull, N. D. and Barnett, N. L. (2002) Antagonists of protein kinase C inhibit rat retinal glutamate transport activity in situ. Journal of Neurochemistry, 81 3: 472-480.


Author Bull, N. D.
Barnett, N. L.
Title Antagonists of protein kinase C inhibit rat retinal glutamate transport activity in situ
Journal name Journal of Neurochemistry   Check publisher's open access policy
Publication date 2002
Sub-type Article
DOI 10.1046/j.1471-4159.2002.00819.x
Volume number 81
Issue number 3
ISSN 0022-3042
Start page 472
End page 480
Total pages 9
Editor Brian Collier
Place of publication UK
Publisher Int. Soc. for Neurochemistry
Collection year 2002
Language eng
Subject C1
270104 Membrane Biology
730111 Hearing, vision, speech and their disorders
Abstract Neuronal and glial high-affinity transporters regulate extracellular glutamate concentration, thereby terminating synaptic transmission and preventing neuronal excitotoxicity. Glutamate transporter activity has been shown to be modulated by protein kinase C (PKC) in cell culture. This is the first study to demonstrate such modulation in situ, by following the fate of the non-metabolisable glutamate transporter substrate, D-aspartate. In the rat retina, pan-isoform PKC inhibition with chelerythrine suppressed glutamate uptake by GLAST (glutamate/aspartate transporter), the dominant excitatory amino acid transporter localized to the glial Muller cells. This effect was mimicked by rottlerin but not by Go6976, suggesting the involvement of the PKCdelta isoform, but not PKCalpha, beta or gamma. Western blotting and immunohistochemical labeling revealed that the suppression of glutamate transport was not due to a change in transporter expression. Inhibition of PKCdelta selectively suppressed GLAST but not neuronal glutamate transporter activity. These data suggest that the targeting of specific glutamate transporters with isoform-specific modulators of PKC activity may have significant implications for the understanding of neurodegenerative conditions arising from compromised glutamate homeostasis, e.g. glaucoma and amyotrophic lateral sclerosis.
Keyword Biochemistry & Molecular Biology
Neurosciences
Excitatory Amino Acid
Excitotoxicity
Glast
Glaucoma
Ischemia
Retina
Amino-acid Transporter-5
Muller Cell
Aspartate Transporter
Transmitter Clearance
Phorbol Esters
Glial-cells
Major Role
Affinity
Expression
Brain
Q-Index Code C1

Document type: Journal Article
Sub-type: Article
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
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