In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 23, No. 11 ( 2003-06-01), p. 4410-4419
Abstract:
Microglia–brain macrophages are immune-competent cells of the CNS and respond to pathologic events. Using bacterial lipopolysaccharide (LPS) as a tool to activate cultured mouse microglia, we studied alterations in the intracellular calcium concentration ([Ca 2+ ] i ) and in the receptor-evoked generation of transient calcium signals. LPS treatment led to a chronic elevation of basal [Ca 2+ ] i along with a suppression of evoked calcium signaling, as indicated by reduced [Ca 2+ ] i transients during stimulation with UTP and complement factor 5a. Presence of the calcium chelator BAPTA prevented the activation-associated changes in [Ca 2+ ] i and restored much of the signaling efficacy. We also evaluated downstream consequences of a basal [Ca 2+ ] i lifting during microglial activation and found BAPTA to strongly attenuate the LPS-induced release of nitric oxide (NO) and certain cytokines and chemokines. Furthermore, microglial treatment with ionomycin, an ionophore elevating basal [Ca 2+ ] i , mimicked the activation-induced calcium signal suppression but failed to induce release activity on its own. Our findings suggest that chronic elevation of basal [Ca 2+ ] i attenuates receptor-triggered calcium signaling. Moreover, increased [Ca 2+ ] i is required, but by itself is not sufficient, for release of NO and certain cytokines and chemokines. Elevation of basal [Ca 2+ ] i could thus prove a central element in the regulation of executive functions in activated microglia.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.23-11-04410.2003
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2003
detail.hit.zdb_id:
1475274-8
SSG:
12
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