Calcium responses mediated by type 2 IP3-receptors are required for osmotic volume regulation of retinal glial cells in mice

Prevention of osmotic swelling of retinal glial (Müller) cells is required to avoid detrimental decreases in the extracellular space volume during intense neuronal activity. Here, we show that glial cells in slices of the wildtype mouse retina maintain the volume of their somata constant up to ∼4 min of perfusion with a hypoosmolar solution. However, calcium chelation with BAPTA/AM induced a rapid swelling of glial cell bodies. In glial cells of retinas from inositol-1,4,5-trisphosphate-receptor type 2-deficient (IP3R2−/−) mice, hypotonic conditions caused swelling of the cell bodies without delay. Exogenous ATP (acting at P2Y1 receptors) prevented the swelling of glial cells in retinal slices from wildtype but not from IP3R2−/− mice. Müller cells from IP3R2−/− mice displayed a strongly reduced amplitude of the ATP-evoked calcium responses as compared to cells from wildtype mice. It is concluded that endogenous calcium signaling mediated by IP3R2 is required for the osmotic volume regulation of retinal glial cells.