title: Acid-sensing channels in human bladder: expression, function and alterations during bladder pain syndrome.
abstract: OBJECTIVE
  We examined the possible role of H(+) activated acid-sensing ion channels in pain perception. We characterized expression in bladder dome biopsies from patients with bladder pain syndrome and controls, in cultured human urothelium and in urothelial TEU-2 cells.
  
  
  METHODS
  Cold cut biopsies from the bladder dome were obtained in 8 asymptomatic controls and 28 patients with bladder pain syndrome symptoms. Acid-sensing ion channel expression was analyzed by quantitative real-time polymerase chain reaction and immunofluorescence. Channel function was measured by electrophysiology.
  
  
  RESULTS
  Acid-sensing ion channel 1a, 2a and 3 mRNA was detected in the human bladder. Similar amounts of acid-sensing ion channel 1a and 3 were detected in detrusor smooth muscle while in urothelium acid-sensing ion channel 3 levels were higher than levels of acid-sensing ion channel 1a. Acid-sensing ion channel 2a mRNA levels were lower than acid-sensing ion channel 1a and 3 levels in each layer. Acid-sensing ion channel currents were measured in TEU-2 cells and in primary cultures of human urothelium. Activated acid-sensing ion channel expression was confirmed by quantitative real-time polymerase chain reaction. TEU-2 cell differentiation caused acid-sensing ion channel 2a and 3 mRNA up-regulation, and acid-sensing ion channel 1a mRNA down-regulation. Patients with bladder pain syndrome showed up-regulation of acid-sensing ion channel 2a and 3 mRNA but acid-sensing ion channel 1a remained unchanged. In contrast, transient receptor potential vanilloid 1 mRNA was down-regulated during bladder pain syndrome. All differences were statistically significant (p <0.05).
  
  
  CONCLUSIONS
  Several acid-sensing ion channel subunits are expressed in human bladder and TEU-2 cells, in which levels are regulated during urothelial differentiation. Up-regulation of acid-sensing ion channel 2a and 3 in patients with bladder pain syndrome suggests involvement in increased pain and hyperalgesia. Down-regulation of transient receptor potential vanilloid 1 mRNA might indicate that a different regulatory mechanism controls its expression in the human bladder.
authors.affiliation: Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, Switzerland.
authors.forename: Verónica
authors.initials: V
authors.lastname: Sánchez-Freire
authors.forename: Maxime G
authors.initials: MG
authors.lastname: Blanchard
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Burkhard
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kessler
authors.forename: Stephan
authors.initials: S
authors.lastname: Kellenberger
authors.forename: Katia
authors.initials: K
authors.lastname: Monastyrskaya
mesh_terms: D062565:Acid Sensing Ion Channels; D000368:Aged; D000584:Amiloride / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D018856:Cystitis, Interstitial / Q000378:metabolism* / Q000503:physiopathology; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism
chemical_list: D062565:Acid Sensing Ion Channels; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C494484:TRPV1 receptor; D000584:Amiloride; D002211:Capsaicin