title: Augmentation of Ca(2+) signaling in astrocytic endfeet in the latent phase of temporal lobe epilepsy.
abstract: Astrocytic endfeet are specialized cell compartments whose important homeostatic roles depend on their enrichment of water and ion channels anchored by the dystrophin associated protein complex (DAPC). This protein complex is known to disassemble in patients with mesial temporal lobe epilepsy and in the latent phase of experimental epilepsies. The mechanistic underpinning of this disassembly is an obvious target of future therapies, but remains unresolved. Here we show in a kainate model of temporal lobe epilepsy that astrocytic endfeet display an enhanced stimulation-evoked Ca(2+) signal that outlast the Ca(2+) signal in the cell bodies. While the amplitude of this Ca(2+) signal is reduced following group I/II metabotropic receptor (mGluR) blockade, the duration is sustained. Based on previous studies it has been hypothesized that the molecular disassembly in astrocytic endfeet is caused by dystrophin cleavage mediated by Ca(2+) dependent proteases. Using a newly developed genetically encoded Ca(2+) sensor, the present study bolsters this hypothesis by demonstrating long-lasting, enhanced stimulation-evoked Ca(2+) signals in astrocytic endfeet.
authors.affiliation: Department of Neurology, Oslo University Hospital Oslo, Norway ; Centre for Molecular Medicine Norway, The Nordic EMBL Partnership, University of Oslo Oslo, Norway ; Letten Centre and GliaLab, Department of Physiology, Institute of Basic Medical Sciences, University of Oslo Oslo, Norway.
authors.forename: Karolina
authors.initials: K
authors.lastname: Szokol
authors.affiliation: Department of Neurology, Oslo University Hospital Oslo, Norway ; Letten Centre and GliaLab, Department of Physiology, Institute of Basic Medical Sciences, University of Oslo Oslo, Norway.
authors.forename: Kjell
authors.initials: K
authors.lastname: Heuser
authors.affiliation: Centre for Molecular Medicine Norway, The Nordic EMBL Partnership, University of Oslo Oslo, Norway ; Letten Centre and GliaLab, Department of Physiology, Institute of Basic Medical Sciences, University of Oslo Oslo, Norway.
authors.forename: Wannan
authors.initials: W
authors.lastname: Tang
authors.affiliation: Centre for Molecular Medicine Norway, The Nordic EMBL Partnership, University of Oslo Oslo, Norway ; Letten Centre and GliaLab, Department of Physiology, Institute of Basic Medical Sciences, University of Oslo Oslo, Norway.
authors.forename: Vidar
authors.initials: V
authors.lastname: Jensen
authors.affiliation: Department of Neurology, Oslo University Hospital Oslo, Norway ; Centre for Molecular Medicine Norway, The Nordic EMBL Partnership, University of Oslo Oslo, Norway ; Letten Centre and GliaLab, Department of Physiology, Institute of Basic Medical Sciences, University of Oslo Oslo, Norway.
authors.forename: Rune
authors.initials: R
authors.lastname: Enger
authors.affiliation: Institute of Cellular Neurosciences, University of Bonn Bonn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bedner
authors.affiliation: Institute of Cellular Neurosciences, University of Bonn Bonn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Steinhäuser
authors.affiliation: Department of Neurology, Oslo University Hospital Oslo, Norway.
authors.forename: Erik
authors.initials: E
authors.lastname: Taubøll
authors.affiliation: University President's Office, University of Oslo Oslo, Norway.
authors.forename: Ole Petter
authors.initials: OP
authors.lastname: Ottersen
authors.affiliation: Department of Neurology, Oslo University Hospital Oslo, Norway ; Centre for Molecular Medicine Norway, The Nordic EMBL Partnership, University of Oslo Oslo, Norway ; Letten Centre and GliaLab, Department of Physiology, Institute of Basic Medical Sciences, University of Oslo Oslo, Norway.
authors.forename: Erlend A
authors.initials: EA
authors.lastname: Nagelhus
keywords: GCaMP; astrocytes; dystrophin; glia; kainate; perivascular