TY - JOUR T1 - Calcium-independent astrocytic lipid release modulates neuronal activity through Kv channels JF - bioRxiv DO - 10.1101/2020.01.12.903393 SP - 2020.01.12.903393 AU - Fushun Wang AU - Heather B. Bradshaw AU - Salvador Pena AU - Beata Jablonska AU - Julia Xavier AU - Sheng Gong AU - Baoman Li AU - Devin Chandler-Militello AU - Lane K. Bekar AU - Nathan A. Smith Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/02/14/2020.01.12.903393.abstract N2 - Cumulative data point to a key role of Ca2+-dependent gliotransmitter release as a modulator of neuronal networks. Here, we tested the hypothesis that astrocytes in response to agonist exposure also release lipid modulators through Ca2+-independent phospholipase A2 (iPLA2) activity. We found that cultured rat astrocytes in response to agonist exposure, released Arachidonic Acid (AA) and/or its derivatives, including the endogenous cannabinoid, 2-arachidonoyl-sn-glycerol (2AG) and the prostaglandin PGE2. Surprisingly, buffering of cytosolic Ca2+ was linked to a sharp increase in astrocytic lipid release. In addition, astrocytic release of PGE2 enhanced mEPSPs by inhibiting the opening of neuronal Kv channels in acute brain slices. This study provides the first evidence for the existence of a Ca2+-independent pathway for the release of PGE2 from astrocytes and furthermore demonstrates a functional role for astrocytic lipid release in the modulation of synaptic activity. ER -