Reduced Retinal Function in the Absence of Na(v)1.6
Date
2012-02
Authors
Smith, Benjamin J.
Cote, Patrice D.
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Abstract
Background: Mice with a function-blocking mutation in the Scn8a gene that encodes
Na(v)1.6, a voltage-gated sodium channel (VGSC) isoform normally found in several types
of retinal neurons, have previously been found to display a profoundly abnormal dark
adapted flash electroretinogram. However the retinal function of these mice in light
adapted conditions has not been studied. Methodology/Principal Findings: In the present
report we reveal that during light adaptation these animals are shown to have
electroretinograms with significant decreases in the amplitude of the a-and b-waves. The
percent decrease in the a-and b-waves substantially exceeds the acute effect of VGSC
block by tetrodotoxin in control littermates. Intravitreal injection of CoCl2 or CNQX to
isolate the a-wave contributions of the photoreceptors in littermates revealed that at
high background luminance the cone-isolated component of the a-wave is of the same
amplitude as the a-wave of mutants. Conclusions/Significance: Our results indicate that
Scn8a mutant mice have reduced function in both rod and the cone retinal pathways. The
extent of the reduction in the cone pathway, as quantified using the ERG b-wave, exceeds
the reduction seen in control littermates after application of TTX, suggesting that a
defect in cone photoreceptors contributes to the reduction. Unless the postreceptoral
component of the a-wave is increased in Scn8a mutant mice, the reduction in the b-wave
is larger than can be accounted for by reduced photoreceptor function alone. Our data
suggests that the reduction in the light adapted ERG of Scn8a mutant mice is caused by a
combination of reduced cone photoreceptor function and reduced depolarization of cone ON
bipolar cells. This raises the possibility that Na(v)1.6 augments signaling in cone
bipolar cells.
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Citation
Smith, Benjamin J., and Patrice D. Cote. 2012. "Reduced Retinal Function in the Absence of Na(v)1.6." Plos One 7(2): 31476-e31476.