Abstract
BackgroundThe expression of retinal CaMKII is up-regulated in the retina of the rdta mouse in which rod photoreceptors are genetically ablated. As ionotropic glutamate receptors are known substrates of CAMKII, this study set out to determine if the protein levels of ionotropic glutamate receptors in the rdta mouse retina are also affected.ResultsThe NMDA receptor subunits (NR1, NR2A/B) and the GluR1; AMPA receptor subunit (GluR1) were examined in immunolabeled western blots. The results demonstrate that the amounts of NR1 and NR2A/B receptor subunits are significantly increased in crude synaptic membrane fractions isolated from retinae of the rdta mice when compared to their normal, littermate controls. The GluR1 receptor subunit and its phosphorylation are simultaneously increased in retinae of the rdta mice.ConclusionsThese data indicate that the NMDA receptors and AMPA (GluR1) receptors are altered in the retinae of rdta mice that lack rod photoreceptors. Because the rods are lost at an early stage in development, it is likely that these results are indicative of synaptic reorganization in the retina.
Highlights
The expression of retinal calmodulin-dependent protein kinase II (CaMKII) is up-regulated in the retina of the rdta mouse in which rod photoreceptors are genetically ablated
Non-NMDA receptors, which are stimulated by kainate, AA-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and quisqualate, but not NMDA
Expression of β-actin is increased in the retinal synaptic membrane fraction isolated from the rdta transgenic mouse No differences could be detected in the levels of β-actin in retinal homogenates isolated from rdta mice and their littermate controls, and this molecule was previously used as an internal reference [34]
Summary
The expression of retinal CaMKII is up-regulated in the retina of the rdta mouse in which rod photoreceptors are genetically ablated. As ionotropic glutamate receptors are known substrates of CAMKII, this study set out to determine if the protein levels of ionotropic glutamate receptors in the rdta mouse retina are affected. Two types of ionotropic glutamate receptors have been classified: (1) NMDA receptors, which bind glutamate and the glutamate analogue N-methyl-D-aspartate (NMDA); (2). Non-NMDA receptors, which are stimulated by kainate, AA-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and quisqualate, but not NMDA. Glutamate binding to non-NMDA receptors opens ion channels more permeable to sodium (Na+) and potassium (K+) than calcium (Ca2+). In contrast to the non-NMDA receptors, the high conductance channel associated with the NMDA receptors is permeable to Ca2+ as well as to Na+ and K+. NMDA-gated currents typically have slower kinetics than kainate- and AMPA-gated channels [3]
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