title: The discovery and characterization of a proton-gated sodium current in rat retinal ganglion cells.
abstract: The conduction of acid-evoked currents in central and sensory neurons is now primarily attributed to a family of proteins called acid-sensing ion channels (ASICs). In peripheral neurons, their physiological function has been linked to nociception, mechanoreception, and taste transduction; however, their role in the CNS remains unclear. This study describes the discovery of a proton-gated current in rat retinal ganglion cells termed I(Na(H+)), which also appears to be mediated by ASICs. RT-PCR confirmed the presence of ASIC mRNA (subunits la, 2a, 2b, 3, and 4) in the rat retina. Electrophysiological investigation showed that all retinal ganglion cells respond to rapid extracellular acidification with the activation of a transient Na+ current, the size of which increases with increasing acidification between pH 6.5 and pH 3.0. I(Na(H+)) desensitizes completely in the continued presence of acid, its current-voltage relationship is linear and its reversal potential shifts with E(Na). I(Na(H+)) is reversibly inhibited by amiloride (IC(50), 188 microm) but is resistant to block by TTX (0.5 microm), Cd2+ (100 microm), procaine (10 mm), and is not activated by capsaicin (0.5 microm). I(Na(H+)) is not potentiated by Zn2+ (300 microm) or Phe-Met-Arg-Phe-amide (50microm) but is inhibited by neuropeptide-FF (50microm). Acute application of pH 6.5 to retinal ganglion cells causes sustained depolarization and repetitive firing similar to the trains of action potentials normally associated with current injection into these cells. The presence of a proton-gated current in the neural retina suggests that ASICs may have a more diverse role in the CNS.
authors.affiliation: Neural Injury and Repair Group, Centre for Neuroscience Research, King's College London, Guy's Campus, London, SE1 1UL, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Lilley
authors.forename: Paul
authors.initials: P
authors.lastname: LeTissier
authors.forename: Jon
authors.initials: J
authors.lastname: Robbins
mesh_terms: D062565:Acid Sensing Ion Channels; D000143:Acids / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D045604:Extracellular Fluid / Q000378:metabolism; D005260:Female; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011522:Protons; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology
chemical_list: D062565:Acid Sensing Ion Channels; D000143:Acids; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D011522:Protons; D012333:RNA, Messenger; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D000584:Amiloride; D012964:Sodium; D015032:Zinc