Session Information
Date: Wednesday, June 22, 2016
Session Title: Neurophysiology (non-PD)
Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To study the distribution of acid-sensing ion channel 1a (ASIC1a) in dopaminergic neurons and its role in regulating dopamine release, and to explore its pathogenic role in Parkinson’s disease development.
Background: Parkinson’s disease(PD) is a common neurodegenerative disorder.Acid sensing ion channels blockers exerted neuroprotective effects in a mouse model of PD, implying a role of ASICs in the pathogenesis of PD.
Methods: Immunofluorescence and Confocal Laser Scanning Microscopy(CLSM) were used to observe the distribution of ASICs in MES 23.5 cells; whole cell patch clamp technique was used to test the electronic properties of ASIC1a current; High Performance Liquid Chromatography (HPLC) was used to determine DA level; and Western blot was performed to study the expression of ASIC1a, pCaMKII proteins.
Results: Inhibitors of ASICs Amiloride (Ami) and PcTx1 blocked the acid-induced current in a dose-dependent manner; the current density of ASICs increased after MPP+ (100uM) incubation for 1h. Compared to control group (PH7.4), extracellular application with pH6.0 solution induced a significant increase of DA release (P<0.05), which was diminished by PcTx1 pretreatment; simultaneously, PcTx1 blocked the DA release caused by MPP+ (100uM). Moreover, the intracellular calcium level increased after MPP+ application, and this was blocked by PcTx1. Pretreatment of KN-93 could reverse the ASICs current increase induced by MPP+; In addition, we observed the level of ASIC1 and pCaMKII proteins increased after MPP+ treatment for 24h (P<0.05).
Conclusions: Functional ASIC1a expresses on dopaminergic cells, and intracellular DA may be exhausted by MPP+ due to over activation of ASIC1a through Ca2+-CaMKII pathway. ASIC1 channel may represent as a target for regulating DA release and thereby protection against DA neuron losses.
[1] Schneider JS, Pioli EY, Jianzhong Y, et al. Levodopa improves motor deficits but can further disrupt cognition in a macaque Parkinson model. Mov Disord, 2013,28(5):663-7. [2] Lees AJ, Hardy J, Revesz T. Parkinson’s disease. Lancet, 2009,373(9680):2055-66.
To cite this abstract in AMA style:
Y. Jing, L. Sha, L. Chunfeng, W. Fen. The regulation of ASIC1a on dopamine release and its implication in the pathogenesis of Parkinson’s disease [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/the-regulation-of-asic1a-on-dopamine-release-and-its-implication-in-the-pathogenesis-of-parkinsons-disease/. Accessed June 14, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-regulation-of-asic1a-on-dopamine-release-and-its-implication-in-the-pathogenesis-of-parkinsons-disease/