| 17316398 |
Rojas H, Colina C, Ramos M, Benaim G, Jaffe EH, Caputo C, DiPolo R: 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.
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. |
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