Stretch-induced Ca2+-independent ATP release in hippocampal astrocytes

Abstract

Astrocytic ATP release is essential for brain functions such as synaptic long-term potentiation for learning and memory. However, whether/how ATP is released via exocytosis remains hotly debated. All previous studies of non-vesicular ATP release have used indirect assays. In contrast, two recent papers report vesicular ATP release using more direct assays. In the present work, by using patch-clamped "ATP-sniffer-cells", we re-investigated astrocytic ATP release at single-vesicle resolution in hippocampal astrocytes. Following an "on-cell-like" mechanical stimulus of a single astrocyte, a Ca²⁺-independent single large non-quantal ATP release occurred, in contrast to the Ca²⁺-dependent multiple small quantal ATP release in a chromaffin cell. The mechanical stimulation-induced ATP release from an astrocyte was inhibited by either exposure to a selective antagonist or genetic knock-down of P2 × 7 receptor channels. Functional P2 × 7 channel were expressed in astrocytes in hippocampal brain slices. Thus, in addition to small quantal ATP release, larger non-quantal ATP release depends on P2 × 7 channels in astrocytes.

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