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.
authors.affiliation: Vision Research Center, Department of Ophthalmology, University of Missouri - Kansas City, School of Medicine, 2411 Holmes St., Kansas City, MO 64108, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Kaja
authors.affiliation: Vision Research Center, Department of Ophthalmology, University of Missouri - Kansas City, School of Medicine, 2411 Holmes St., Kansas City, MO 64108, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Payne
authors.affiliation: Vision Research Center, Department of Ophthalmology, University of Missouri - Kansas City, School of Medicine, 2411 Holmes St., Kansas City, MO 64108, USA.
authors.forename: Krupa R
authors.initials: KR
authors.lastname: Patel
authors.affiliation: Vision Research Center, Department of Ophthalmology, University of Missouri - Kansas City, School of Medicine, 2411 Holmes St., Kansas City, MO 64108, USA.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Naumchuk
authors.affiliation: Vision Research Center, Department of Ophthalmology, University of Missouri - Kansas City, School of Medicine, 2411 Holmes St., Kansas City, MO 64108, USA. Electronic address: koulenp@umkc.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Koulen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002110:Caffeine / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009900:Optic Nerve / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011914:Rats, Inbred BN
chemical_list: D002110:Caffeine
keywords: Calcium channel; Calcium imaging; Drug discovery; Glaucoma; Optic nerve; Optic nerve head astrocyte; Primary cell culture