| First Author | Wang DJ | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 8 | Pages | e41499 |
| PubMed ID | 22927908 | Mgi Jnum | J:191686 |
| Mgi Id | MGI:5462313 | Doi | 10.1371/journal.pone.0041499 |
| Citation | Wang DJ, et al. (2012) Cytosolic phospholipase A2 alpha/arachidonic acid signaling mediates depolarization-induced suppression of excitation in the cerebellum. PLoS One 7(8):e41499 |
| abstractText | 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. 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 Ca(2+)-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. |
