Na+ entry via glutamate transporter activates the reverse Na+/Ca2+ exchange and triggers Ca(i)2+-induced Ca2+ release in rat cerebellar Type-1 astrocytes

J Neurochem. 2007 Mar;100(5):1188-202. doi: 10.1111/j.1471-4159.2006.04303.x.


We have previously demonstrated that rat cerebellar Type-1 astrocytes express a very active genistein sensitive Na(+)/Ca(2+) exchanger, which accounts for most of the total plasma membrane Ca(2+) fluxes and for the clearance of loads induced by physiological agonists. In this work, we have explored the mechanism by which the reverse Na(+)/Ca(2+) exchange is involved in agonist-induced Ca(2+) signaling in rat cerebellar astrocytes. Microspectrofluorometric measurements of Cai(2+) with Fluo-3 demonstrate that the Cai(2+) signals associated long (> 20 s) periods of reverse operation of the Na(+)/Ca(2+) exchange are amplified by a mechanism compatible with calcium-calcium release, while those associated with short (< 20 s) pulses are not amplified. This was confirmed by pharmacological experiments using ryanodine receptors agonist (4-chloro-m-cresol) and the endoplasmic reticulum ATPase inhibitor (thapsigargin). Confocal microscopy demonstrates a high co-localization of immunofluorescent labeled Na(+)/Ca(2+) exchanger and RyRs. Low (< 50 micromol/L) or high (> 500 micromol/L) concentrations of L-glutamate (L-Glu) or L-aspartate causes a rise in which is completely blocked by the Na(+)/Ca(2+) exchange inhibitors KB-R7943 and SEA0400. The most important novel finding presented in this work is that L-Glu activates the reverse mode of the Na(+)/Ca(2+) exchange by inducing Na(+) entry through the electrogenic Na(+)-Glu-co-transporter and not through the ionophoric L-Glu receptors, as confirmed by pharmacological experiments with specific blockers of the ionophoric L-Glu receptors and the electrogenic Glu transporter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport System X-AG / physiology*
  • Animals
  • Astrocytes / metabolism*
  • Calcium / metabolism
  • Calcium / physiology*
  • Calcium Signaling
  • Cations
  • Cerebellum / metabolism*
  • Fluorescent Antibody Technique
  • In Vitro Techniques
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Rats
  • Rats, Sprague-Dawley
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Sodium / metabolism*
  • Sodium-Calcium Exchanger / metabolism*
  • Spectrometry, Fluorescence


  • Amino Acid Transport System X-AG
  • Cations
  • Ryanodine Receptor Calcium Release Channel
  • Sodium-Calcium Exchanger
  • Sodium
  • Calcium