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The ability of O(2) levels to regulate Ca(2+) signalling in non-excitable cells is poorly understood, yet crucial to our understanding of Ca(2+)-dependent cell functions in physiological and pathological situations. Here, we demonstrate that hypoxia mobilizes Ca(2+) from an intracellular pool in primary cultures of cortical astrocytes. This pool can also be mobilized by bradykinin, which acts via phospholipase C and inositol trisphosphate production. By contrast, hypoxic Ca(2+) mobilization utilizes ryanodine receptors, which appear to be either present on the same intracellular pool, or on a separate but functionally coupled pool. Hypoxic activation of ryanodine receptors requires formation of cyclic ADP ribose, since hypoxic Ca(2+) mobilization was fully prevented by nicotinamide (which inhibits ADP ribosyl cyclase) or by 8-Br-cADP ribose, an antagonist of cyclic ADP ribose. Our results demonstrate for the first time the involvement of cyclic ADP ribose in hypoxic modulation of Ca(2+) signalling in the central nervous system, and suggest that this modulator of ryanodine receptors may play a key role in the function of astrocytes under conditions of fluctuating O(2) levels.

Original publication

DOI

10.1016/j.ceca.2005.09.009

Type

Journal article

Journal

Cell Calcium

Publication Date

01/2006

Volume

39

Pages

95 - 100

Keywords

ADP-ribosyl Cyclase, Animals, Astrocytes, Bradykinin, Calcium, Calcium Signaling, Cell Hypoxia, Cells, Cultured, Cyclic ADP-Ribose, Niacinamide, Oxygen, Rats, Ryanodine Receptor Calcium Release Channel, Type C Phospholipases