title: Effect of activation of the Ca(2+)-permeable acid-sensing ion channel 1a on focal cerebral ischemia in diabetic rats.
abstract: We investigated the role of acid-sensing ion channel Ia (ASIC1a) expression and changes in intracellular Ca(2+) concentration ([Ca(2+)]) in focal cerebral ischemia after middle cerebral artery occlusion (MCAO) in a rat model of diabetes mellitus (DM). Male Wistar rats (n = 108) were divided into three groups: the MCAO, DM + MCAO, and DM + MCAO + fasudil groups (n = 36 each). Samples were obtained 1, 3, 6, and 24 h after ischemia induction (n = 9). Rats in the DM + MCAO + fasudil group were treated with 1 mg/kg fasudil, a Rho-kinase inhibitor, by caudal vein injection 30 min after MCAO was performed. ASIC1a expression gradually increased with time in the MCAO and DM + MCAO groups (0.71 ± 0.10 nM, 0.80 ± 0.11 nM, 0.86 ± 0.08 nM, 0.93 ± 0.09 nM; 0.86 ± 0.11 nM, 1.05 ± 0.51 nM, 2.42 ± 0.08 nM, 2.78 ± 0.04 nM; pairwise comparisons at each time point, P < 0.05), and was higher in the DM + MCAO than the MCAO group (P < 0.05). [Ca(2+)] gradually increased in the DM + MCAO group (106.32 ± 18.6 nM, 137.84 ± 14.32 nM, 151.94 ± 18.38 nM, 183.61 ± 7.96 nM, P < 0.05). ASIC1a expression and calcium currents were reduced in the DM + MCAO + fasudil group. The overload of intracellular [Ca(2+)] caused by ASIC1a activation could be one mechanism for the aggravation of focal cerebral ischemia in diabetes.
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University Changchun 130033, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, China-Japan Union Hospital, Jilin University Changchun 130033, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Wen
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University Changchun 130033, China.
authors.forename: Cui-Cui
authors.initials: CC
authors.lastname: Cui
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University Changchun 130033, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xing
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D062565:Acid Sensing Ion Channels / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000378:metabolism*; D008297:Male; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D062565:Acid Sensing Ion Channels; C568268:Asic1 protein, rat; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil; D002118:Calcium
keywords: Cerebral ischemia; brain injury; calcium channel