The Activity of the Na⁺/Ca²⁺ Exchanger Largely Modulates the Ca²⁺_i Signal Induced by Hypo-Osmotic Stress in Rat Cerebellar Astrocytes. The Effect of Osmolarity on Exchange Activity

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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⁺ signalling 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 hypo-tonicity, 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. Interestingly, 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 and decreased in hypertonic solutions. 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.