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

1. The subcellular characteristics of an ATP-induced elevation of the cytoplasmic free calcium concentration ([Ca2+](i)) were studied in cul tured cells of the oligodendrocyte lineage obtained from mouse cortex and rabbit retina, as well as in oligodendrocytes from mouse corpus ca llosum slices, using laser scanning confocal microfluorometry. 2. With the stage- and lineage-specific antibodies O4 and O10, three developm ental stages within the oligodendrocyte lineage were distinguished pri or to Ca2+ recording. 3. Bath application of 1-100 mu M ATP induced a transient increase of [Ca2+](i) in late precursors and oligodendrocyte s but not in early glial precursor cells from retinal and cortical cul tures 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 hi gher in processes as compared with the soma; in cortical cultures such an uneven response was only observed in oligodendrocytes, while in im mature cells responses in soma and processes were of similar amplitude . 5. The rank order of potency for the purine and pyrimidine nucleotid es 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, indica ting the involvement of a P-2-purinoreceptor in the ATP-mediated [Ca2](i) response. 6. ATP-induced elevation of the cytosolic Ca2+ concentr ation was inhibited by incubating cells with thapsigargin (10 mu M) an d by intracellular administration of heparin (1 mu M). These findings indicate that ATP triggers a release of Ca2+ ions from InsP(2)-sensiti ve internal stores. 7. The ATP receptors may play a role in neuron-gli al signal transfer; ATP is released as neurotransmitter, but also unde r pathological conditions from damaged cells.