Subcellular propagation of calcium waves in Müller glia does not require autocrine/paracrine purinergic signaling.

The polarized morphology of radial glia allows them to functionally interconnect different layers of CNS tissues including the retina, cerebellum, and cortex. A likely mechanism involves propagation of transcellular Ca2+ waves which were proposed to involve purinergic signaling. Because it is not known whether ATP release is required for astroglial Ca2+ wave propagation we investigated this in mouse Müller cells, radial astroglia-like retinal cells in which in which waves can be induced and supported by Orai/TRPC1 (transient receptor potential isoform 1) channels. We found that depletion of endoplasmic reticulum (ER) stores triggers regenerative propagation of transcellular Ca2+ waves that is independent of ATP release and activation of P2 X and P2 Y receptors. Both the amplitude and kinetics of transcellular, depletion-induced waves were resistant to non-selective purinergic P2 antagonists such as pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). Thus, store-operated calcium entry (SOCE) is itself sufficient for the initiation and subcellular propagation of calcium waves in radial glia.