Extracellular ATP release predominantly mediates Ca2+ communication locally in highly organised, stellate-Like patterned networks of adult human astrocytes

Abstract

The ‘Astrocyte Network’ and the understanding of its communication has been posed as a new grand challenge to be investigated by contemporary science. However, communication studies in astrocyte networks have investigated traditional petri-dishin vitroculture models where cells are closely packed and can deviate from the stellate form observed in the brain. Using novel cell patterning approaches, highly organised, regular grid networks of astrocytes on chip, to single-cell fidelity are constructed, permitting a stellate-likein vitronetwork model to be realised. By stimulating the central cell with a single UV nanosecond laser pulse, the initiation/propagation pathways of stellate-like networks are re-explored. The authors investigate the mechanisms of intercellular Ca2+communication and discover that stellate-like networks of adult human astrocytesin vitroactually exploit extracellular ATP release as their dominant propagation pathway to cells in the network locally; being observed even down to the nearest neighbour and next nearest neighbouring cells—contrary to the reported gap junction. This discovery has significant ramifications to many neurological conditions such as epilepsy, stroke and aggressive astrocytomas where gap junctions can be targeted. In cases where such gap junction targeting has failed, this new finding suggests that these conditions should be re-visited and the ATP transmission pathway targeted instead.