ACTIVATION OF P-2-PURINORECEPTORS TRIGGERED CA2+ RELEASE FROM INSP(3)-SENSITIVE INTERNAL STORES IN MAMMALIAN OLIGODENDROCYTES

1. The subcellular characteristics of an ATP-induced elevation of the cytoplasmic free calcium concentration ([Ca2+](i)) were studied in cultured cells of the oligodendrocyte lineage obtained from mouse cortex and rabbit retina, as well as in oligodendrocytes from mouse corpus callosum slices, using laser scanning confocal microfluorometry. 2. With the stage- and lineage-specific antibodies O4 and O10, three developmental stages within the oligodendrocyte lineage were distinguished prior to Ca2+ recording. 3. Bath application of 1-100 mu M ATP induced a transient increase of [Ca2+](i) in late precursors and oligodendrocytes but not in early glial precursor cells from retinal and cortical cultures and from corpus callosum slices. This effect of ATP was observed in Ca2+-free extracellular solution, suggesting that the ATP-mediated elevation of [Ca2+](i) is due to a Ca2+ liberation from intracellular stores. 4. In both late precursors and oligodendrocytes from retina, the amplitude of ATP-induced [Ca2+](i) transients was significantly higher in processes as compared with the soma; in cortical cultures such an uneven response was only observed in oligodendrocytes, while in immature cells responses in soma and processes were of similar amplitude. 5. The rank order of potency for the purine and pyrimidine nucleotides was UTP greater than or equal to ATP > ADP >> AMP = adenosine = Me-ATP for retinal oligodendrocytes, and ADP greater than or equal to ATP >> UTP = AMP = adenosine = Me-ATP for cortical oligodendrocytes. The response to ATP and related nucleotides was blocked by suramin, indicating the involvement of a P-2-purinoreceptor in the ATP-mediated [Ca2+](i) response. 6. ATP-induced elevation of the cytosolic Ca2+ concentration was inhibited by incubating cells with thapsigargin (10 mu M) and by intracellular administration of heparin (1 mu M). These findings indicate that ATP triggers a release of Ca2+ ions from InsP(2)-sensitive internal stores. 7. The ATP receptors may play a role in neuron-glial signal transfer; ATP is released as neurotransmitter, but also under pathological conditions from damaged cells.