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The Journal of Neuroscience, May 18, 2005, 25(20):5046-5050; doi:10.1523/JNEUROSCI.4692-04.2005

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BRIEF COMMUNICATION
Physiological Maturation of Photoreceptors Depends on the Voltage-Gated Sodium Channel Na_V1.6 (Scn8a)

Patrice D. Côté,¹ Yves De Repentigny,¹ Stuart G. Coupland,² Yannick Schwab,³ Michel J. Roux,³ S. Rock Levinson,⁴ and Rashmi Kothary^1,5

¹Molecular Medicine Program, Ottawa Health Research Institute, and University of Ottawa Center for Neuromuscular Disease, Ottawa, Ontario, Canada K1H 8L6, ²Vision Program, Ottawa Health Research Institute, and University of Ottawa Eye Institute, Ottawa, Ontario, Canada K1H 8L6, ³Laboratoire de Physiopathologie Moléculaire et Cellulaire de la Rétine, Institut National de la Santé et de la Recherche Médicale U592, Institut de Génétique et de Biologie Cellulaire et Moléculaire, 67404 Illkirch Cedex, France, ⁴Physiology and Biophysics, University of Colorado Health Sciences Center, Denver, Colorado 80262, and ⁵Departments of Medicine and Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5

Voltage-gated sodium channels (VGSCs) ensure the saltatory propagation of action potentials along axons by acting as signal amplifiers at the nodes of Ranvier. In the retina, activity mediated by VGSCs is important for the refinement of the retinotectal map. Here, we conducted a full-field electroretinogram (ERG) study on mice null for the sodium channel Na_V1.6. Interestingly, the light-activated hyperpolarization of photoreceptor cells (the a-wave) and the major "downstream" components of the ERG, the b-wave and the oscillatory potentials, are markedly reduced and delayed in these mice. The functional deficit was not associated with any morphological abnormality. We demonstrate that Scn8a is expressed in the ganglion and inner nuclear layers and at low levels in the outer nuclear layer beginning shortly before the observed ERG deficit. Together, our data reveal a previously unappreciated role for VGSCs in the physiological maturation of photoreceptors.

Key words: voltage-gated sodium channel; Na_V1.6; Scn8a; retina; photoreceptors; electroretinogram; development

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Received Nov 16, 2004; revised April 8, 2005; accepted April 14, 2005.

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