Inhibition of Na+/Ca2+ exchange enhances delayed neuronal death elicited by glutamate in cerebellar granule cell cultures

Andreeva, N. A.; Bi, Khodorov; Stelmashook, E. V.; Cragoe, Edward J.; Victorov, Ilya V.

doi:10.1016/0006-8993(91)91141-m

Cited by 121 publications

(58 citation statements)

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“…Primary cerebellar cultures were prepared from the cerebella of 7-8-day-old Wistar rats using a procedure described earlier [12]. The initial potassium concentration in the medium was 5 mM; on the second day of cultivation the potassium concentration was increased to 25 mM.…”

Section: Methodsmentioning

confidence: 99%

Neurotoxic glutamate treatment of cultured cerebellar granule cells induces Ca²⁺‐dependent collapse of mitochondrial membrane potential and ultrastructural alterations of mitochondria

et al. 1996

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Rhodamine 123 staining and electron microscopy were used to reveal a correlation between the ultrastructural and functional state of cultured cerebellar granule cells after short glutamate treatment. Glutamate exposure (15 min, 100 lxM) in Mg2+-free solution caused considerable ultrastructural alterations in a granule cell: clumping of the chromatin, swelling of the endoplasmic reticulum and mitochondria, and disruption of the mitochondrial cristae. After glutamate treatment, the mitochondria of the neurons lost their ability to sequester rhodamine 123. Both the N-methyl-D-nspartate receptor channel blocker MK-801 (30 ItM) and cobalt chloride (2 mM) prevented the deteriorative effects of glutamate. These data suggest that glutaumte-induced Ca 2+ overload of the neurons can lead to nonspecific permeability of the inner mitochondrial membrane, resulting in neuronal death.

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Section: Methodsmentioning

confidence: 99%

Neurotoxic glutamate treatment of cultured cerebellar granule cells induces Ca²⁺‐dependent collapse of mitochondrial membrane potential and ultrastructural alterations of mitochondria

et al. 1996

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“…Dissociated cerebellar granule cell cultures were prepared from the cerebella of 7-8-day-old Wistar rats using the procedure described in [3]. The cultures were incubated in a medium with 25 mM K + throughout the whole cultivation period.…”

Section: Methodsmentioning

confidence: 99%

Dominant role of mitochondria in protection against a delayed neuronal Ca²⁺ overload induced by endogenous excitatory amino acids following a glutamate pulse

Pinelis

Storozhevykh

et al. 1996

FEBS Letters

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The objective of this study was to evaluate the contribution of mitochondria to the clearance of Ca 2+ loads induced by glutamate or 25 mM K ÷ pulses. The mitochondrial Ca 2+ uptake was suppressed by application of 0.5 ttM antimycin A or 3-5 mM NaCN in combination with 2.5 Ixg/ml oligomycin. In most cells such treatments both in the presence and in the absence of external Na + failed to abolish the early fast phase of

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“…Several groups reported that NCX blockers rescue both neurons and glia from hypoxia/reoxygenation or glutamate-induced injury [112][113][114]. However, the others found increased cell death upon NCX inhibition [115,116]. Of special interest is the involvement of NCX in white matter injury (reviewed in [14]).…”

Section: Pathological Roles For Na + /H + Exchange: Impact On [Na + ]mentioning

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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Inhibition of Na+/Ca2+ exchange enhances delayed neuronal death elicited by glutamate in cerebellar granule cell cultures

Cited by 121 publications

References 11 publications

Neurotoxic glutamate treatment of cultured cerebellar granule cells induces Ca²⁺‐dependent collapse of mitochondrial membrane potential and ultrastructural alterations of mitochondria

Neurotoxic glutamate treatment of cultured cerebellar granule cells induces Ca²⁺‐dependent collapse of mitochondrial membrane potential and ultrastructural alterations of mitochondria

Dominant role of mitochondria in protection against a delayed neuronal Ca²⁺ overload induced by endogenous excitatory amino acids following a glutamate pulse

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

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Inhibition of Na+/Ca2+ exchange enhances delayed neuronal death elicited by glutamate in cerebellar granule cell cultures

Cited by 121 publications

References 11 publications

Neurotoxic glutamate treatment of cultured cerebellar granule cells induces Ca2+‐dependent collapse of mitochondrial membrane potential and ultrastructural alterations of mitochondria

Neurotoxic glutamate treatment of cultured cerebellar granule cells induces Ca2+‐dependent collapse of mitochondrial membrane potential and ultrastructural alterations of mitochondria

Dominant role of mitochondria in protection against a delayed neuronal Ca2+ overload induced by endogenous excitatory amino acids following a glutamate pulse

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

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Neurotoxic glutamate treatment of cultured cerebellar granule cells induces Ca²⁺‐dependent collapse of mitochondrial membrane potential and ultrastructural alterations of mitochondria

Neurotoxic glutamate treatment of cultured cerebellar granule cells induces Ca²⁺‐dependent collapse of mitochondrial membrane potential and ultrastructural alterations of mitochondria

Dominant role of mitochondria in protection against a delayed neuronal Ca²⁺ overload induced by endogenous excitatory amino acids following a glutamate pulse