期刊
PLOS ONE
卷 7, 期 8, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0041499
关键词
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资金
- National Basic Research Program (973) of the Ministry of Science and Technology of China [2009CB94140, 2011CB5044000]
- National Foundation of Natural Science of China [30600168, 31070945, 31100780]
- National Foundation of Natural Science [30731160616]
- Research Grants Council of Hong Kong, China [30731160616]
- Ministry of Education of China [NCET-07-0751]
- Zhejiang Provincial Foundation of Natural Science of China [R206018]
Background: Depolarization-induced suppression of excitation (DSE) at parallel fiber-Purkinje cell synapse is an endocannabinoid-mediated short-term retrograde plasticity. Intracellular Ca2+ elevation is critical for the endocannabinoid production and DSE. Nevertheless, how elevated Ca2+ leads to DSE is unclear. Methodology/Principal Findings: We utilized cytosolic phospholipase A(2) alpha (cPLA(2)alpha) knock-out mice and whole-cell patch clamp in cerebellar slices to observed the action of cPLA(2)alpha/arachidonic acid signaling on DSE at parallel fiber-Purkinje cell synapse. Our data showed that DSE was significantly inhibited in cPLA(2)alpha knock-out mice, which was rescued by arachidonic acid. The degradation enzyme of 2-arachidonoylglycerol (2-AG), monoacylglycerol lipase (MAGL), blocked DSE, while another catabolism enzyme for N-arachidonoylethanolamine (AEA), fatty acid amide hydrolase (FAAH), did not affect DSE. These results suggested that 2-AG is responsible for DSE in Purkinje cells. Co-application of paxilline reversed the blockade of DSE by internal K+, indicating that large conductance Ca2+-activated potassium channel (BK) is sufficient to inhibit cPLA(2)alpha/arachidonic acid-mediated DSE. In addition, we showed that the release of 2-AG was independent of soluble NSF attachment protein receptor (SNARE), protein kinase C and protein kinase A. Conclusions/Significance: Our data first showed that cPLA(2)alpha/arachidonic acid/2-AG signaling pathway mediates DSE at parallel fiber-Purkinje cell synapse.
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