Norepinephrine-induced calcium signaling in astrocytes in the respiratory network of the ventrolateral medulla

Respir Physiol Neurobiol. 2016 Jun;226:18-23. doi: 10.1016/j.resp.2015.10.008. Epub 2015 Nov 2.


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.

Keywords: Catecholaminergic signaling; Glia; Neuronal control of breathing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism
  • Enzyme Inhibitors / pharmacology
  • Indoles / pharmacology
  • Inositol Phosphates / metabolism
  • Medulla Oblongata / cytology
  • Medulla Oblongata / drug effects
  • Medulla Oblongata / metabolism*
  • Mice, Transgenic
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Norepinephrine / metabolism*
  • Potassium / metabolism
  • Respiration* / drug effects
  • Sodium Channel Blockers / pharmacology
  • Tetrodotoxin / pharmacology
  • Tissue Culture Techniques
  • Type C Phospholipases / metabolism
  • Voltage-Sensitive Dye Imaging


  • Enzyme Inhibitors
  • Indoles
  • Inositol Phosphates
  • Sodium Channel Blockers
  • inositol trispyrophosphate
  • Tetrodotoxin
  • Type C Phospholipases
  • Potassium
  • Calcium
  • Norepinephrine
  • cyclopiazonic acid