Leaky receptors in stressed brains

Jones, Rachel

doi:10.1038/nrn3356

Research Highlight
Published: 20 September 2012

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Leaky receptors in stressed brains

Rachel Jones

Nature Reviews Neuroscience volume 13, page 668 (2012)Cite this article

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Ryanodine receptors on the endoplasmic reticulum contribute to intracellular calcium release and are important for calcium homeostasis in neurons and other types of cell. In heart cells, chronic stress conditions lead to phosphorylation, oxidation and nitrosylation of the type 2 ryanodine receptor (RYR2) calcium release channels so that they become unbound from the subunit calstabin 2 and subsequently become 'leaky' — they release excessive intracellular calcium, which damages cardiac cells. RYR2s are also expressed in hippocampal neurons, so the authors investigated whether stress-induced hippocampal damage was mediated by these channels.

Liu et al. used chronic restraint to induce stress in mice and discovered that RYR2s in the hippocampi of these mice were phosphorylated by protein kinase A, oxidated and nitrosylated, just as in heart cells. Binding of calstabin 2 to the channels was reduced, and they became leaky. The mice also showed impaired cognitive performance in various behavioural tests, such as the Morris water maze, that are known to depend on hippocampal function, and long-term potentiation (LTP) was reduced in their hippocampi.

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ORIGINAL RESEARCH PAPER

Liu, X. et al. Role of leaky neuronal ryanodine receptors in stress-induced cognitive dysfunction. Cell 150, 1055–1067 (2012)
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