2008 Volume 58 Issue 4 Pages 277-290
We recently demonstrated that rat cerebellar Type-1 astrocytes express a very active Na+/Ca2+ exchanger highly colocalized with ryanodine receptors (RyRs), which in turn play a key role in glutamate-induced Ca2+ signaling through a calcium-induced calcium release (CICR) mechanism. In this work we have explored whether the Na+/Ca2+ exchanger has any role in the Ca2+ i signal induced by hypo-osmotic stress in these cells, using microspectrofluorometric measurements with Fura-2, pharmacological tools, and confocal microscopy image analysis. We present evidence for the first time that the increase in [Ca2+]i in rat cerebellar Type-1 astrocytes, resulting from moderate hypotonic shock, is mediated by Ca2+ release from ryanodine-operated Ca2+ i stores, and that the magnitude of the intracellular Ca2+ signal induced by hypotonicity in the short term (up to 240 s) is small and controlled by the activity of the Na+/Ca2+ exchanger operating in its extrusion mode. With longer times in the hypotonic medium, intracellular Ca2+ store depletion leads to Ca2+ entry through store-operated Ca2+ channels. We found it interesting that the activity of the Na+/Ca2+ exchanger measured during this reverse mode operation (Ca2+ entry in exchange for internal Na+) was found to be greatly increased in hypotonic solutions and decreased in hypertonic ones. The buffering of the [Ca2+] i rise induced by hypo-osmotic stress may prevent excessive increases in [Ca2+]i, which otherwise might impair the normal function of this glial cell.