Calcium-Independent Astrocytic Lipid Release Modulates Neuronal Activity Through Kv Channels

Cumulative data point to a key role of Ca 2+ -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 Ca 2+ -independent phospholipase A 2 (iPLA 2 ) 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 E2 (PGE 2 ). Surprisingly, buffering of cytosolic Ca 2+ was linked to a sharp increase in astrocytic lipid release. In addition, astrocytic release of PGE 2 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 Ca 2+ -independent pathway for the release of PGE 2 from astrocytes and furthermore demonstrates a functional role for astrocytic lipid release in the modulation of synaptic activity.