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Li + protects nerve cells against destabilization of Ca 2+ homeostasis and delayed death caused by removal of external Na +
Author(s) -
Khodorov B.,
Pinelis V.,
Vinskaya N.,
Sorokina E.,
Grigortsevich N.,
Storozhevykh T.
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00350-6
Subject(s) - chemistry , homeostasis , glutamate receptor , calcium , biophysics , stereochemistry , biochemistry , receptor , endocrinology , biology , organic chemistry
In experiments with fura‐2 loaded cultured rat cerebellar granule cells we have compared the changes in [Ca 2+ ] 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 [Ca 2+ ] i and a considerable delay in [Ca 2+ ] i recovery following a glutamate (Glu) pulse in almost all the cells. In contrast Na + /Li + replacement usually did not change baseline [Ca 2+ ] i and produced only a small (if any) delay in the post‐glutamate [Ca 2+ ] i recovery. Previously [Storozhevykh et al. (1998) FEBS Lett. 431, 215–218] we revealed that perturbation of [Ca 2+ ] i homeostasis caused by Na + /NMDG replacement cannot be explained by a reversal of the Na + /Ca 2+ exchange but is mainly due to Ca 2+ 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 [Ca 2+ ] i homeostasis and delayed neuronal death caused by Na + /NMDG replacement. Li + is also able to abolish the [Ca 2+ ] 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 [Ca 2+ ] i increase caused by PDC. Control experiments showed that Na + /Li + replacement does not decrease the [Ca 2+ ] 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 [Ca 2+ ] 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 + .