Dynorphin opioid peptides enhance acid-sensing ion channel 1a activity and acidosis-induced neuronal death.
Dynorphin opioid peptides enhance acid-sensing ion channel 1a activity and acidosis-induced neuronal death.
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DOI：
10.1523/jneurosci.2186-09.2009
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发表时间：
2009-11-11
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影响因子：
--
通讯作者：
Askwith CC
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文献类型：
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作者：
Sherwood TW;Askwith CC
Acid sensing ion channel 1a (ASIC1a) promotes neuronal damage during pathological acidosis. ASIC1a undergoes a process called steady-state desensitization in which incremental pH reductions desensitize the channel and prevent activation when the threshold for acid-dependent activation is reached. 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, non-opioid, target for dynorphin action and suggest that dynorphins enhance neuronal damage following ischemia by preventing steady-state desensitization of ASIC1a.
