title: Acid-sensing ion channel 1a is involved in retinal ganglion cell death induced by hypoxia.
abstract: OBJECTIVE
  Loss of retinal ganglion cells (RGCs) during retinal ischemia is the potentially blinding mechanism that underlies several sight-threatening disorders. Fluctuations in extracellular pH are associated with such pathological conditions. It has been demonstrated that the retina is a functionally distinct region of central neurons that are known to contain acid-sensing ion channels (ASICs), which are depolarizing conductance channels directly activated by protons. This study was conducted to determine whether ASIC1a channels in RGCs are essential for ischemia-induced cell death.
  
  
  METHODS
  Expression of ASIC1a channels was detected in primary cultures of rat RGCs and in retinal sections. The patch-clamp technique in the conventional whole-cell configuration was used to examine the currents evoked by acid in the cultured RGCs. Intracellular Ca(2+) ([Ca(2+)]i) elevation was detected by Ca(2+) imaging. Furthermore, hypoxia-induced cell death in RGC cultures was measured by methyl thiazolyl tetrazolium assay.
  
  
  RESULTS
  RGCs expressed a high density of ASIC1a channels. The expression and function of ASIC1a channels were upregulated after hypoxia in cultured RGCs. Ratiometric Ca(2+) imaging showed that RGCs responding to a drop in pH presented an increase in the concentration of (Ca(2+))i. Acute blockade of ASIC1a channels with the specific inhibitor amiloride or psalmotoxin 1 reduced RGC death in vitro.
  
  
  CONCLUSIONS
  Based on these novel findings, we conclude that ASIC1a plays a role in RGC death induced by hypoxia. Therefore, neuroprotective strategies in glaucoma could include tools to improve the ability of these neurons to survive the cytotoxic consequences of ASIC1a activation.
authors.affiliation: Department of plastic surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Tan
authors.forename: Xinhai
authors.initials: X
authors.lastname: Ye
authors.forename: Yipin
authors.initials: Y
authors.lastname: Xu
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Minjie
authors.initials: M
authors.lastname: Sheng
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
mesh_terms: D062565:Acid Sensing Ion Channels; D000143:Acids / Q000378:metabolism*; D000200:Action Potentials / Q000187:drug effects; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia; D015870:Gene Expression / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D057054:Molecular Imaging; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010455:Peptides; D061251:Primary Cell Culture; D051381:Rats; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D012966:Sodium Cyanide; D013111:Spider Venoms / Q000494:pharmacology
chemical_list: D062565:Acid Sensing Ion Channels; D000143:Acids; D009419:Nerve Tissue Proteins; C413209:PcTX1 protein, Psalmopoeus cambridgei; D010455:Peptides; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013111:Spider Venoms; D000584:Amiloride; D012966:Sodium Cyanide; D002118:Calcium