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We find that dynorphin A and big dynorphin limit steady-state desensitization of ASIC1a and acid-activated currents in cortical neurons. Dynorphin potentiation of ASIC1a activity is independent of opioid or bradykinin receptor activation but is prevented in the presence of PcTx1, a peptide which is known to bind the extracellular domain of ASIC1a. This suggests that dynorphins interact directly with ASIC1a to enhance channel activity. Inducing steady-state desensitization prevents ASIC1a-mediated cell death during prolonged acidosis. This neuroprotection is abolished in the presence of dynorphins. Together, these results define ASIC1a as a new nonopioid target for dynorphin action and suggest that dynorphins enhance neuronal damage following ischemia by preventing steady-state desensitization of ASIC1a.<\/jats:p>","DOI":"10.1523\/jneurosci.2186-09.2009","type":"journal-article","created":{"date-parts":[[2009,11,11]],"date-time":"2009-11-11T18:28:01Z","timestamp":1257964081000},"page":"14371-14380","source":"Crossref","is-referenced-by-count":125,"title":["Dynorphin Opioid Peptides Enhance Acid-Sensing Ion Channel 1a Activity and Acidosis-Induced Neuronal Death"],"prefix":"10.1523","volume":"29","author":[{"given":"Thomas W.","family":"Sherwood","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candice 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