title: Norepinephrine-induced calcium signaling in astrocytes in the respiratory network of the ventrolateral medulla.
abstract: The neuronal activity in the respiratory network of the ventrolateral medulla strongly depends on a variety of different neuromodulators. Since the respiratory activity generated by neurons in the pre-Bötzinger complex (preBötC) is stabilized by astrocytes, we investigated potential effects of the neuromodulator norepinephrine (NE) on the astrocytic calcium signaling in the ventral respiratory group. In acutely isolated brainstem slices from wild type mice (postnatal day 1-10) we performed calcium imaging experiments using Oregon Green 488 BAPTA-1 AM as a calcium indicator dye. Astrocytes in the preBötC, which were identified by their unique intracellular calcium rise after the reduction of the extracellular K(+) concentration, showed calcium rises in response to norepinephrine. These calcium signals persisted after blockade of neuronal activity by tetrodotoxin (TTX) indicating that they were independent of neuronal activity. Furthermore, application of the endoplasmic reticulum calcium pump blocker cyclopiazonic acid (CPA) diminished norepinephrine-induced calcium signals. This results could be confirmed using transgenic mice with astrocyte specific expression of GCaMP3. Thus, norepinephrine might, apart from acting directly on neurons, influence and modulate respiratory network activity via the modulation of astroglial calcium signaling.
authors.affiliation: DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany; Divisions of Pathophysiology & Repair and Neuroscience, School of Biosciences, Cardiff University, Cardiff, United Kingdom.
authors.forename: Christian
authors.initials: C
authors.lastname: Schnell
authors.affiliation: Clinic for Anesthesiology, University Hospital Göttingen, 37099 Göttingen, Germany.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Negm
authors.affiliation: Clinic for Anesthesiology, University Hospital Göttingen, 37099 Göttingen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Driehaus
authors.affiliation: Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of Saarland, Homburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Scheller
authors.affiliation: DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany; Clinic for Anesthesiology, University Hospital Göttingen, 37099 Göttingen, Germany. Electronic address: shuelsm2@uni-goettingen.de.
authors.forename: Swen
authors.initials: S
authors.lastname: Hülsmann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D012119:Respiration / Q000187:drug effects; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D046509:Tissue Culture Techniques; D010738:Type C Phospholipases / Q000378:metabolism; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D007295:Inositol Phosphates; D026941:Sodium Channel Blockers; C516441:inositol trispyrophosphate; D013779:Tetrodotoxin; D010738:Type C Phospholipases; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine; C000543:cyclopiazonic acid
keywords: Catecholaminergic signaling; Glia; Neuronal control of breathing