Protease activated receptor 1-induced glutamate release in cultured astrocytes is mediated by Bestrophin-1 channel but not by vesicular exocytosis

Mol Brain. 2012 Oct 12:5:38. doi: 10.1186/1756-6606-5-38.

Abstract

Background: Glutamate is the major transmitter that mediates the principal form of excitatory synaptic transmission in the brain. It has been well established that glutamate is released via Ca2+-dependent exocytosis of glutamate-containing vesicles in neurons. However, whether astrocytes exocytose to release glutamate under physiological condition is still unclear.

Findings: We report a novel form of glutamate release in astrocytes via the recently characterized Ca2+-activated anion channel, Bestrophin-1 (Best1) by Ca2+ dependent mechanism through the channel pore. We demonstrate that upon activation of protease activated receptor 1 (PAR1), an increase in intracellular Ca2+ concentration leads to an opening of Best1 channels and subsequent release of glutamate in cultured astrocytes.

Conclusions: These results provide strong molecular evidence for potential astrocyte-neuron interaction via Best1-mediated glutamate release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anions
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Bestrophins
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / metabolism
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Cytoplasmic Vesicles / drug effects
  • Cytoplasmic Vesicles / metabolism*
  • Exocytosis* / drug effects
  • Eye Proteins / metabolism*
  • Fluorescence Resonance Energy Transfer
  • Glutamic Acid / metabolism*
  • Ion Channels / metabolism*
  • Mice
  • Oligopeptides / pharmacology
  • Receptor, PAR-1 / metabolism*

Substances

  • Anions
  • Best1 protein, mouse
  • Bestrophins
  • Calcium Channel Blockers
  • Calcium Channels
  • Eye Proteins
  • Ion Channels
  • Oligopeptides
  • PAR-1-activating peptide
  • Receptor, PAR-1
  • Glutamic Acid