title: Acid-sensing ion channels in healthy and degenerated human intervertebral disc.
abstract: Acid-sensing ion channels (ASICs) are a family of H(+)-gated voltage-insensitive ion channels that respond to extracellular acidification by regulating transmembrane Ca(2+) flux. Moreover, ASICs can also be gated by mechanical forces and may function as mechanosensors. The cells of the intervertebral disc (IVD) have an unusual acidic and hyperosmotic microenvironment. Changes in the pH and osmolarity determine the viability of IVD cells and the composition of the extracellular matrix, and both are the basis of IVD degeneration. In this study, the expression of ASICs (ASIC1, ASIC2, ASIC3 and ASIC4) mRNAs and proteins in human healthy and degenerated IVD was evaluated by quantitative reverse transcription-quantitative polymerase chain reaction and Western blot. The distribution of ASIC proteins was determined by immunohistochemistry. The mRNAs for all ASICs were detected in normal human IVD, and significantly increased levels were found in degenerated IVD. Western blots demonstrated the presence of proteins with estimated molecular weights of approximately 68-72 kDa. In both the annulus fibrosus (AF) and nucleus pulposus (NP) of normal IVD, ASIC2 is the most frequently expressed ASIC followed by ASIC3, ASIC1 and ASIC4. In the AF of degenerated IVD, there was a significant increase in the number of ASIC1 and ASIC4 positive cells, whereas in the NP, we found significant increase of expression of ASIC1, ASIC2 and ASIC3. These results describe the occurrence and localization of different ASICs in human healthy IVD, and their increased expression in degenerated IVD, thus suggesting that ASICs may be involved in IVD degeneration.
authors.affiliation: Departamento de Morfología y Biología Celular and.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuesta
authors.forename: Miguel E
authors.initials: ME
authors.lastname: Del Valle
authors.forename: Olivia
authors.initials: O
authors.lastname: García-Suárez
authors.forename: Eliseo
authors.initials: E
authors.lastname: Viña
authors.forename: Roberto
authors.initials: R
authors.lastname: Cabo
authors.forename: Gorka
authors.initials: G
authors.lastname: Vázquez
authors.forename: Juan L
authors.initials: JL
authors.lastname: Cobo
authors.forename: Antonio
authors.initials: A
authors.lastname: Murcia
authors.forename: Marco
authors.initials: M
authors.lastname: Alvarez-Vega
authors.forename: José
authors.initials: J
authors.lastname: García-Cosamalón
authors.forename: José A
authors.initials: JA
authors.lastname: Vega
mesh_terms: D062565:Acid Sensing Ion Channels / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002118:Calcium / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*
chemical_list: D062565:Acid Sensing Ion Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D002118:Calcium