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

Abstract

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 E2 (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.