Differential subcellular Ca2+ signaling in a highly specialized subpopulation of astrocytes Journal Article

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Authors: Kaja, S.; Payne, A. J.; Patel, K. R.; Naumchuk, Y.; Koulen, P.
Article Title: Differential subcellular Ca2+ signaling in a highly specialized subpopulation of astrocytes
Abstract: Recent evidence suggests that astrocytes do not serve a mere buffering function, but exhibit complex signaling pathways, disturbance of which contributes significantly to the pathophysiology of CNS diseases. Little is known regarding the intracellular signaling pathways in the specialized optic nerve head astrocytes (ONHAs), the major glia cell type in non-myelinated optic nerve head. Here we show the differential subcellular expression of intracellular Ca(2+) channels in ONHAs. Expression of type 1 and type 3 inositol-1-4-5,-trisphosphate receptors (IP3Rs) in the endoplasmic reticulum and type 2 IP3Rs in the nuclear envelope causes differential Ca(2+) release from intracellular stores in nuclear vs. cytosolic compartments. Our study identifies differential distribution and activity of Ca(2+) channels as molecular substrate and mechanism by which astrocytes independently regulate Ca(2+) transients in both cytoplasm and nucleoplasm, thereby controlling genomic and non-genomic cellular signaling, respectively. This provides excellent targets for therapeutics restoring pathological disturbances of intracellular Ca(2+) signaling present in glaucoma and other neurodegenerative disorders with astrocyte involvement.
Journal Title: Experimental neurology
Volume: 265
ISSN: 1090-2430; 0014-4886
Publisher: Elsevier Inc  
Journal Place: United States
Date Published: 2015
Start Page: 59
End Page: 68
Language: ENG
DOI/URL:

10.1016/j.expneurol.2014.12.014
Notes: LR: 20161019; CI: Copyright (c) 2014; GR: P01 AG022550/AG/NIA NIH HHS/United States; GR: P01 AG027956/AG/NIA NIH HHS/United States; GR: AG010485/AG/NIA NIH HHS/United States; GR: R01 EY014227/EY/NEI NIH HHS/United States; GR: AG022550/AG/NIA NIH HHS/United States; GR: P01 AG010485/AG/NIA NIH HHS/United States; GR: EY014227/EY/NEI NIH HHS/United States; GR: R01 EY022774/EY/NEI NIH HHS/United States; GR: EY022774/EY/NEI NIH HHS/United States; GR: RR022570/RR/NCRR NIH HHS/United States; GR: AG027956/AG/NIA NIH HHS/United States; GR: S10 RR027093/RR/NCRR NIH HHS/United States; GR: S10 RR022570/RR/NCRR NIH HHS/United States; GR: RR027093/RR/NCRR NIH HHS/United States; JID: 0370712; 3G6A5W338E (Caffeine); NIHMS651817; OID: NLM: NIHMS651817; OID: NLM: PMC4346429; OTO: NOTNLM; 2014/10/10 [received]; 2014/11/26 [revised]; 2014/12/12 [accepted]; ppublish