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- Title
Inhibition of glutamate-induced delayed calcium deregulation by 2-APB and La<sup>3+</sup> in cultured cortical neurones.
- Authors
Chinopoulos, Christos; Gerencser, Akos A.; Doczi, Judit; Fiskum, Gary; Adam-Vizi, Vera
- Abstract
Exposure of neurones in culture to excitotoxic levels of glutamate results in an initial transient spike in [Ca2+]i followed by a delayed, irreversible [Ca2+]i rise governed by rapid kinetics, with Ca2+ originating from the extracellular medium. The molecular mechanism responsible for the secondary Ca2+ rise is unknown. Here, we report that the delayed Ca2+ entry in cortical neurones is diminished by 2-aminoethoxydiphenyl borate (2-APB: IC50 = 62 ± 9 μM) and La3+ (IC50 = 7.2 ± 3 μM), both known to inhibit transient receptor potential (TRP) and store-operated Ca2+ (SOC) channels. Application of thapsigargin, however, failed to exacerbate the delayed Ca2+ deregulation, arguing against a store depletion event as the stimulus for induction of the secondary [Ca2+]i rise. In addition, these neurones did not exhibit SOC entry. Unexpectedly, application of ryanodine or caffeine significantly inhibited glutamate-induced delayed Ca2+ deregulation. In basal Ca2+ entry experiments, La3+ and 2-APB modulated the rapid rise in [Ca2+]i caused by exposure of neurones to Ca2+ after pre-incubating in a calcium-free medium. This basal Ca2+ influx was mitigated by extracellular Mg2+ but not aggravated by thapsigargin, ryanodine or caffeine. These results indicate that 2-APB and La3+ influence non-store-operated Ca2+ influx in cortical neurones and that this route of Ca2+ entry is involved in glutamate-induced delayed Ca2+ deregulation.
- Subjects
NEURONS; NERVOUS system; GLUTAMINE; CALCIUM; AMINO acids; NEURAL receptors; NERVE endings
- Publication
Journal of Neurochemistry, 2004, Vol 91, Issue 2, p471
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2004.02732.x