1. Archive
2. Vol.58, No.4

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

Abstract: 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.

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