title: Silencing acid-sensing ion channel 1a alters cone-mediated retinal function.
abstract: 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.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6097, Universtité de Nice-Sophia Antipolis, Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Ettaiche
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Deval
authors.forename: Marc
authors.initials: M
authors.lastname: Cougnon
authors.forename: Michel
authors.initials: M
authors.lastname: Lazdunski
authors.forename: Nicolas
authors.initials: N
authors.lastname: Voilley
mesh_terms: D062565:Acid Sensing Ion Channels; D000200:Action Potentials / Q000502:physiology* / Q000528:radiation effects; D000818:Animals; D001683:Biological Clocks / Q000502:physiology* / Q000528:radiation effects; D020868:Gene Silencing; D008027:Light; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010775:Photic Stimulation; D051381:Rats; D012160:Retina / Q000502:physiology / Q000528:radiation effects; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology* / Q000528:radiation effects; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: D062565:Acid Sensing Ion Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015222:Sodium Channels