Li+ protects nerve cells against destabilization of Ca2+ homeostasis and delayed death caused by removal of external Na+
| Autor: | E. G. Sorokina, N. Grigortsevich, T. P. Storozhevykh, Pinelis Vg, N. Vinskaya, B. I. Khodorov |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Programmed cell death
N-Methylaspartate Stereochemistry Biophysics Endogeny Lithium Biochemistry Structural Biology Neurotoxicity Genetics medicine Animals Homeostasis Viability assay Rats Wistar Molecular Biology Cells Cultured Neurons Calcium metabolism Cell Death Chemistry Cultured neuron Sodium Na+/Ca2+ exchange Glutamate receptor Cell Biology medicine.disease Rats NMDA receptor Calcium Glutamate |
| Zdroj: | FEBS Letters. 448:173-176 |
| ISSN: | 0014-5793 |
| DOI: | 10.1016/s0014-5793(99)00350-6 |
| Popis: | In experiments with fura-2 loaded cultured rat cerebellar granule cells we have compared the changes in [Ca2+]i homeostasis produced by replacement of external Na+ with the organic cation N-methyl-d-glucamine (NMDG) or Li+. The Na+/NMDG replacement caused an increase in baseline [Ca2+]i and a considerable delay in [Ca2+]i recovery following a glutamate (Glu) pulse in almost all the cells. In contrast Na+/Li+ replacement usually did not change baseline [Ca2+]i and produced only a small (if any) delay in the post-glutamate [Ca2+]i recovery. Previously [Storozhevykh et al. (1998) FEBS Lett. 431, 215–218] we revealed that perturbation of [Ca2+]i homeostasis caused by Na+/NMDG replacement cannot be explained by a reversal of the Na+/Ca2+ exchange but is mainly due to Ca2+ influx through NMDA channels activated by Na+ dependent release of endogenous excitatory amino acids (`reversed Glu uptake'). In the present work we confirmed this conclusion and obtained evidence suggesting that in contrast to NMDG Li+ interferes with the `reversed Glu uptake' triggered by removal of external Na+. Thus it has been shown that the addition of Li+ (20 mM) to a Na+-free NMDGcontaining solution suppressed both the perturbation of [Ca2+]i homeostasis and delayed neuronal death caused by Na+/NMDG replacement. Li+ is also able to abolish the [Ca2+]i response induced by PDC which at high concentrations (>200 μM) is shown to stimulate the release of endogenous Glu. In contrast to Na+/Li+, Na+/NMDG replacement greatly enhances [Ca2+]i increase caused by PDC. Control experiments showed that Na+/Li+ replacement does not decrease the [Ca2+]i response to the Glu pulse. Therefore we concluded that a considerable quantitative difference between the effects of Na+/NMDG and Na+/Li+ replacements on both [Ca2+]i homeostasis and cell viability resulted mainly from the ability of Li+ to attenuate the release of endogenous Glu in response to the removal of external Na+. |
| Databáze: | OpenAIRE |
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