ASICs aggravate acidosis-induced injuries during ischemic reperfusion.
Although acidosis is considered as a byproduct of brain ischemia, its effect on neurons during ischemia and reperfusion remains controversial, and the exact role of acid-sensing ion channels (ASICs) is unclear. Here we investigated the effect of acidosis on hippocampal neurons and the role of ASICs during both oxygen-glucose deprivation (OGD) and reperfusion. MTT assay and annexin V/PI staining suggested that although acidosis had a negative effect during OGD, it was more detrimental during reperfusion. Furthermore, inhibition of ASICs, especially ASIC1a, protected hippocampal neurons from acidotic injuries. Data from whole-cell patch clamp recordings also indicated that acute OGD did not alter the ASIC-current amplitude or desensitization comparing with normoxia conditions, however, it delayed the recovery of ASICs from desensitization. This result partially explained the failure of amiloride and PcTx1 in protecting neurons during acidotic OGD. Collectively, our study demonstrated that the result of the severe damage caused by acidosis during reperfusion but not during OGD was partially due to the different recovery time of ASICs between reperfusion and OGD.
Gu
Ling
L
Department of Biomedical Engineering, Key Laboratory of Biomedical Engineering, Ministry of Education, Zhejiang University, Hangzhou, PR China.
Liu
Xiaoyu
X
Yang
Yi
Y
Luo
Dijun
D
Zheng
Xiaoxiang
X
D062565:Acid Sensing Ion Channels; D000138:Acidosis / Q000188:drug therapy / Q000503:physiopathology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005947:Glucose / Q000172:deficiency* / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology*; D015222:Sodium Channels / Q000378:metabolism*; D013997:Time Factors
D062565:Acid Sensing Ion Channels; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D005947:Glucose