title: Cytosolic phospholipase A2 alpha/arachidonic acid signaling mediates depolarization-induced suppression of excitation in the cerebellum.
abstract: BACKGROUND
  Depolarization-induced suppression of excitation (DSE) at parallel fiber-Purkinje cell synapse is an endocannabinoid-mediated short-term retrograde plasticity. Intracellular Ca(2+) elevation is critical for the endocannabinoid production and DSE. Nevertheless, how elevated Ca(2+) leads to DSE is unclear.
  
  
  RESULTS
  We utilized cytosolic phospholipase A(2) alpha (cPLA(2)α) knock-out mice and whole-cell patch clamp in cerebellar slices to observed the action of cPLA(2)α/arachidonic acid signaling on DSE at parallel fiber-Purkinje cell synapse. Our data showed that DSE was significantly inhibited in cPLA(2)α 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 Ca(2+)-activated potassium channel (BK) is sufficient to inhibit cPLA(2)α/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
  Our data first showed that cPLA(2)α/arachidonic acid/2-AG signaling pathway mediates DSE at parallel fiber-Purkinje cell synapse.
authors.affiliation: Key Laboratory of Medical Neurobiology of the Ministry of Health, Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: De-Juan
authors.initials: DJ
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.forename: Li-Da
authors.initials: LD
authors.lastname: Su
authors.forename: Ya-jun
authors.initials: YJ
authors.lastname: Xie
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Cheng-Long
authors.initials: CL
authors.lastname: Sun
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D055724:Electrophysiological Phenomena / Q000187:drug effects; D063388:Endocannabinoids / Q000378:metabolism; D055786:Gene Knockout Techniques; D005989:Glycerides / Q000378:metabolism; D054513:Group IV Phospholipases A2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011689:Purkinje Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D007211:Indoles; D026902:Potassium Channel Blockers; D016718:Arachidonic Acid; C048220:paxilline; C094503:glyceryl 2-arachidonate; D054513:Group IV Phospholipases A2; D011188:Potassium; D002118:Calcium