4.6 Article

Tonic extracellular glutamate and ischaemia: glutamate antiporter system xc- regulates anoxic depolarization in hippocampus

Journal

JOURNAL OF PHYSIOLOGY-LONDON
Volume 601, Issue 3, Pages 607-629

Publisher

WILEY
DOI: 10.1113/JP283880

Keywords

ambient glutamate; cystine/glutamate transporter; excitotoxicity; stroke

Ask authors/readers for more resources

Stroke-induced release of glutamate triggers anoxic depolarization (AD) and rapid cell death. Tonic glutamate, regulated by the system x(c)(-), has a significant effect on the latency of AD events and subsequent tissue damage. Transgenic mice lacking the system x(c)(-) exhibit longer AD latencies and altered depolarizing waves after oxygen deprivation, highlighting the role of ambient glutamate in the pathogenesis of acute stroke.
In stroke, the sudden deprivation of oxygen to neurons triggers a profuse release of glutamate that induces anoxic depolarization (AD) and leads to rapid cell death. Importantly, the latency of the glutamate-driven AD event largely dictates subsequent tissue damage. Although the contribution of synaptic glutamate during ischaemia is well-studied, the role of tonic (ambient) glutamate has received far less scrutiny. The majority of tonic, non-synaptic glutamate in the brain is governed by the cystine/glutamate antiporter, system x(c)(-). Employing hippocampal slice electrophysiology, we showed that transgenic mice lacking a functional system x(c)(-) display longer latencies to AD and altered depolarizing waves compared to wild-type mice after total oxygen deprivation. Experiments which pharmacologically inhibited system x(c)(-), as well as those manipulating tonic glutamate levels and those antagonizing glutamate receptors, revealed that the antiporter's putative effect on ambient glutamate precipitates the ischaemic cascade. As such, the current study yields novel insight into the pathogenesis of acute stroke and may direct future therapeutic interventions.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available