In:
Science Signaling, American Association for the Advancement of Science (AAAS), Vol. 2, No. 93 ( 2009-10-20)
Abstract:
Excessive cytosolic calcium ion (Ca 2+ ) accumulation during cerebral ischemia triggers neuronal cell death, but the underlying mechanisms are poorly understood. Capacitive Ca 2+ entry (CCE) is a process whereby depletion of intracellular Ca 2+ stores causes the activation of plasma membrane Ca 2+ channels. In nonexcitable cells, CCE is controlled by the endoplasmic reticulum (ER)–resident Ca 2+ sensor STIM1, whereas the closely related protein STIM2 has been proposed to regulate basal cytosolic and ER Ca 2+ concentrations and make only a minor contribution to CCE. Here, we show that STIM2, but not STIM1, is essential for CCE and ischemia-induced cytosolic Ca 2+ accumulation in neurons. Neurons from Stim2 −/− mice showed significantly increased survival under hypoxic conditions compared to neurons from wild-type controls both in culture and in acute hippocampal slice preparations. In vivo, Stim2 −/− mice were markedly protected from neurological damage in a model of focal cerebral ischemia. These results implicate CCE in ischemic neuronal cell death and establish STIM2 as a critical mediator of this process.
Type of Medium:
Online Resource
ISSN:
1945-0877
,
1937-9145
DOI:
10.1126/scisignal.2000522
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2009
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