Antagonists of protein kinase C inhibit rat retinal glutamate transport activity in situ
Article first published online: 29 APR 2002
Journal of Neurochemistry
Volume 81, Issue 3, pages 472–480, May 2002
How to Cite
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: 472–480. doi: 10.1046/j.1471-4159.2002.00819.x
- Issue published online: 29 APR 2002
- Article first published online: 29 APR 2002
- Received September 6, 2001; revised manuscript received October 26, 2001; accepted January 7, 2002.
- excitatory amino acid;
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 Müller cells. This effect was mimicked by rottlerin but not by Gö6976, suggesting the involvement of the PKCδ isoform, but not PKCα, β or γ. Western blotting and immunohistochemical labeling revealed that the suppression of glutamate transport was not due to a change in transporter expression. Inhibition of PKCδ 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.