Swelling-induced release of glutamate, aspartate, and taurine from astrocyte cultures

Kimelberg, Harold K.; Goderie, Susan K.; Higman, Susan M.; Pang, S.F.; Waniewski, RA

doi:10.1523/jneurosci.10-05-01583.1990

Cited by 670 publications

(402 citation statements)

References 58 publications

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“…Kimelberg and colleagues [14,18] have demonstrated that hyposmotic media cause a cell swelling-dependent, calciumindependent release of EAAs from astrocytes. To ask whether bradykinin might utilize such a mechanism we monitored astrocyte volume using BCECF.…”

Section: Resultsmentioning

confidence: 99%

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α‐Latrotoxin stimulates glutamate release from cortical astrocytes in cell culture

et al. 1995

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The mechanism responsible for the ability of bradykinin to cause calcium-dependent release of glutamate from astrocytes in vitro was investigated. The glutamate transport inhibitor, dihydrokainate, did not block bradykinin-induced glutamate release, and bradykinin did not cause cell swelling. These data exclude the involvement of glutamate transporters or swelling mechansims as mediating glutamate release in response to bradykinin, a-Latrotoxin (3 nM), a component of black widow spider venom, stimulated calcium-independent glutamate release from astrocytes. Since c~-latrotoxin induces vesicle fusion and calcium-independent neuronal neurotransmitter release, our data suggest that astrocytes may release neurotransmitter using a mechanism similar to the neuronal secretory process.

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Section: Resultsmentioning

confidence: 99%

“…Fax: (1) operation of a glutamate transporter [13], (ii) release through a swelling-induced pathway [14], or (iii) a calcium-dependent vesicle release mechanism [15]. In this study we have investigated the mechanism responsible for controlling release of neurotransmitter from astrocytes.…”

Section: Introductionmentioning

confidence: 99%

α‐Latrotoxin stimulates glutamate release from cortical astrocytes in cell culture

et al. 1995

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“…The precise reasons for such selective susceptibility of astrocytes to ischemic swelling are unknown; several hypothetical mechanisms are discussed elsewhere [13,45]. A key study that proposed a mechanistic link between astrocytic swelling and brain damage has been done by Kimelberg and co-workers, who found that exposure of cultured astrocytes to hypoosmotic media triggers massive release of several cytosolic amino acids, including glutamate and aspartate [52]. The swellingactivated amino acid release permeability pathway is sensitive to a number of anion channel blockers, and has strong similarities to the already mentioned swelling-activated anion channel VRAC [22,24,[52][53][54].…”

Section: Volume-regulated Anion Channels and The Reversed Mode Of Glumentioning

confidence: 99%

“…A key study that proposed a mechanistic link between astrocytic swelling and brain damage has been done by Kimelberg and co-workers, who found that exposure of cultured astrocytes to hypoosmotic media triggers massive release of several cytosolic amino acids, including glutamate and aspartate [52]. The swellingactivated amino acid release permeability pathway is sensitive to a number of anion channel blockers, and has strong similarities to the already mentioned swelling-activated anion channel VRAC [22,24,[52][53][54]. Since electrophysiological studies confirmed that VRAC possesses measurable permeability to glutamate and aspartate [55][56][57], this channel has long been considered a hypothetical pathway for pathological release of excitotoxins from swollen cells [13,45,46].…”

Section: Volume-regulated Anion Channels and The Reversed Mode Of Glumentioning

confidence: 99%

Disruption of ionic and cell volume homeostasis in cerebral ischemia: The perfect storm

Mongin

2007

Pathophysiology

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The mechanisms of brain tissue damage in stroke are strongly linked to the phenomenon of excitotoxicity, which is defined as damage or death of neural cells due to excessive activation of receptors for the excitatory neurotransmitters glutamate and aspartate. Under physiological conditions, ionotropic glutamate receptors mediate the processes of excitatory neurotransmission and synaptic plasticity. In ischemia, sustained pathological release of glutamate from neurons and glial cells causes prolonged activation of these receptors, resulting in massive depolarization and cytoplasmic Ca 2+ overload. The NMDA subtype of glutamate receptors is particularly important as it represents the main initial route for the Ca 2+ influx. High cytoplasmic levels of Ca 2+ activate many degradative processes that, depending on the metabolic status, cause immediate or delayed death of neural cells. This traditional view has been expanded by a number of observations that implicate Cl − channels and several types of non-channel transporter proteins, such as the Na + ,K + ,2Cl − cotransporter, Na + /H + exchanger, and Na + /Ca 2+ exchanger, in the development of glutamate toxicity. Some of these ion transporters increase tissue damage by promoting pathological cell swelling and necrotic cell death, while others contribute to a long term accumulation of cytoplasmic Ca 2+ . This brief review is aimed at illustrating how the dysregulation of various ion transport processes combine in a 'perfect storm' that disrupts neural ionic homeostasis and culminates in the irreversible damage and death of neural cells. The clinical relevance of individual transporters as targets for therapeutic intervention in stroke is also briefly discussed.

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“…Furthermore, prevention of brain edema in rats with ALF has been shown with ammonia-lowering strategies (Cordoba et al, 1999;Rose et al, 1999Rose et al, , 2000. Unrelated to ammonia, swelling-induced glutamate release was demonstrated in cortical astrocytes exposed to a hypo-osmotic medium (Kimelberg et al, 1990). Ammonia-induced astrocytic swelling has been suggested to result in glutamine accumulation in astrocytes (by glutamine synthetase), possibly because of the inhibition of glutaminase (Bradford et al, 1989).…”

Section: Calcium-independent Glutamate Releasementioning

confidence: 99%

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Rose

2002

Metabolic Brain Disease

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Glutamatergic dysfunction has been suggested to play an important role in the pathogenesis of hepatic encephalopathy (HE) in acute liver failure (ALF). Increased extracellular brain glutamate concentrations have consistently been described in different experimental animal models of ALF and in patients with increased intracranial pressure due to ALF. High brain ammonia levels remain the leading candidate in the pathogenesis of HE in ALF and studies have demonstrated a correlation between ammonia and increased concentrations of extracellular brain glutamate both clinically and in experimental animal models of ALF. Inhibition of glutamate uptake or increased glutamate release from neurons and/or astrocytes could cause an increase in extracellular glutamate. This review analyses the effect of ammonia on glutamate release from (and uptake into) both neurons and astrocytes and how these pathophysiological mechanisms may be involved in the pathogenesis of HE in ALF.

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Swelling-induced release of glutamate, aspartate, and taurine from astrocyte cultures

Cited by 670 publications

References 58 publications

α‐Latrotoxin stimulates glutamate release from cortical astrocytes in cell culture

α‐Latrotoxin stimulates glutamate release from cortical astrocytes in cell culture

Disruption of ionic and cell volume homeostasis in cerebral ischemia: The perfect storm

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