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The Journal of Neuroscience, May 24, 2006, 26(21):5800-5809; doi:10.1523/JNEUROSCI.0344-06.2006
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Cellular/Molecular
Silencing Acid-Sensing Ion Channel 1a Alters Cone-Mediated Retinal Function
Mohammed Ettaiche, Emmanuel Deval, Marc Cougnon, Michel Lazdunski, andNicolas Voilley Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6097, Universtité de Nice-Sophia Antipolis, Institut Paul Hamel, Sophia Antipolis, 06560 Valbonne, France
Correspondence should be addressed to Prof. Michel Lazdunski, Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6097, Universtité de Nice-Sophia Antipolis, Institut Paul Hamel, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France. Email: ipmc{at}ipmc.cnrs.fr
The action of extracellular protons on retinal activity and phototransduction occurs through pH-sensitive elements, mainly membrane conductances present on the different cell types of the outer and inner nuclear layers and of the ganglion cell layer. Acid-sensing ion channels (ASICs) are depolarizing conductances that are directly activated by protons. We investigated the participation of ASIC1a, a particular isoform of ASICs, in retinal physiology in vivo using electroretinogram measurements. In situ hybridization and immunohistochemistry localized ASIC1a in the outer and inner nuclear layers (cone photoreceptors, horizontal cells, some amacrine and bipolar cells) and in the ganglion cell layer. Both the in vivo knockdown of ASIC1a by antisense oligonucleotides and the in vivo blocking of its activity by PcTx1, a specific venom peptide, were able to decrease significantly and reversibly the photopic a- and b-waves and oscillatory potentials. Our study indicates that ASIC1a is an important channel in normal retinal activity. Being present in the inner segments of cones and inner nuclear layer cells, and mainly at synaptic cleft levels, it could participate in gain adaptation to ambient light of the cone pathway, facilitating cone hyperpolarization in brightness and modulating synaptic transmission of the light-induced visual signal.
Key words: acid-sensing ion channel; retina; ASIC1a; cone photoreceptor; pH; proton-gated current
Received Aug. 10, 2005; revised April 3, 2006; accepted April 3, 2006.
Correspondence should be addressed to Prof. Michel Lazdunski, Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6097, Universtité de Nice-Sophia Antipolis, Institut Paul Hamel, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France. Email: ipmc{at}ipmc.cnrs.fr
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