Ca(2+) Entry is Required for Mechanical Stimulation-induced ATP Release from Astrocyte

Exp Neurobiol. 2015 Mar;24(1):17-23. doi: 10.5607/en.2015.24.1.17. Epub 2015 Mar 13.

Abstract

Astrocytes and neurons are inseparable partners in the brain. Neurotransmitters released from neurons activate corresponding G protein-coupled receptors (GPCR) expressed in astrocytes, resulting in release of gliotransmitters such as glutamate, D-serine, and ATP. These gliotransmitters in turn influence neuronal excitability and synaptic activities. Among these gliotransmitters, ATP regulates the level of network excitability and is critically involved in sleep homeostasis and astrocytic Ca(2+) oscillations. ATP is known to be released from astrocytes by Ca(2+)-dependent manner. However, the precise source of Ca(2+), whether it is Ca(2+) entry from outside of cell or from the intracellular store, is still not clear yet. Here, we performed sniffer patch to detect ATP release from astrocyte by using various stimulation. We found that ATP was not released from astrocyte when Ca(2+) was released from intracellular stores by activation of Gαq-coupled GPCR including PAR1, P2YR, and B2R. More importantly, mechanical stimulation (MS)-induced ATP release from astrocyte was eliminated when external Ca(2+) was omitted. Our results suggest that Ca(2+) entry, but not release from intracellular Ca(2+) store, is critical for MS-induced ATP release from astrocyte.

Keywords: ATP; Astrocytes; Ca2+; Mechanical stimulation.