CHARACTERIZATION OF RYANODINE RECEPTORS IN OLIGODENDROCYTES, TYPE-2 ASTROCYTES, AND O-2A PROGENITORS

In this study we have investigated the expression of ryanodine recepto rs (RyRs), and the ability of caffeine to evoke RyR-mediated elevation of intracellular Ca2+ levels ([Ca2+](i)) in glial cells of the oligod endrocyte/ type 2 astrocyte lineage. Immunocytochemistry with specific antibodies identified ryanodine receptors in cultured oligodendrocyte s, type 2 astrocytes, and O-2A progenitor cells, at high levels in the perinuclear region and in a variegated pattern along processes, Glia acutely isolated from rat brain and in aldehyde-fixed sections of cort ex were similarly found to express RyRs. Caffeine (5-50 mM) caused an increase in [Ca2+](i) in most cultured type 2 astrocytes and in 50% of oligodendrocytes. Responses elicited by caffeine were inhibited by pr etreatment with ryanodine (10 mu M) or thapsigargin (1 mu M), and the peak response was unaffected by removal of [Ca2+](O). O-2A progenitor cells, in contrast, were largely unresponsive to caffeine treatment. P retreatment with kainate (200 mu M) to activate Ca2+ entry increased t he magnitude of caffeine-evoked [Ca2+](i) elevations in type 2 astrocy tes and oligodendrocytes, and caused caffeine to activate responses in a significant proportion of previously non-responding O-2A progenitor s. In both type 2 astrocytes and oligodendrocytes, caffeine evoked Ca2 + changes which propagated as wavefronts from several initiation sites , These wave amplification sites were characterized by significantly h igher local Ca2+ release kinetics. Our results indicate that several g Lial cell types express RyRs, and that their functionality differs wit hin different cell types of the oligodendrocyte Lineage. In addition, ionotropic glutamate receptor activation fills the caffeine-sensitive Ca2+ stores in these cells. (C) 1998 Wiley-Liss, Inc.