[Mechanisms of neuronal calcium homeostasis destabilization caused by hyperstimulation of glutamate receptors].
The present paper summarizes the data obtained in studying the mechanisms of glutamate-induced deterioration of neuronal Ca2+ homeostasis. In the cultured mammalian central neurons, a short-term (< 1 min) glutamate (GLU, 100 mu) challenge is known to induce a readily reversible (transient) neuronal [Ca2+]i increase. In contrast, a long-term (15-30 min) GLU exposure leads to the appearance of high [Ca2+]i plateau or to the partial recovery of the increased [Ca2+]i. Experiments show that impaired [Ca2+]i recovery in the postglutamate period cannot be explained by the increased [Ca2+]i permeability of the neuronal membrane, as earlier considered. Moreover, a sustained elevation of [Ca2+]i during and after chronic GLU application is associated with a progressive decrease in Ca2+ permeability. The major cause of GLU-induced Ca2+ overload is the mitochondrial depolarization resulted from excessive Ca2+ influx into the mitochondria, the generation of free radicals and the opening of a "giant pore" in the inner mitochondrial membrane. This in turn suppresses both ATP synthesis and Ca2+ electrophoretic uptake into the mitochondrial matrix. In combination with [Ca2+]i-dependent acidification, this leads to the suppression of Ca2+ release from the cell via Na+/Ca2+ exchanger and Ca2+/H+ pump of the neuronal membrane. Therefore, [Ca2+]i recovery following a long-term GLU treatment becomes strongly or even irreversibly compromised.
B I
BI
Khodorov
V G
VG
Pinelis
I V
IV
Viktorov
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D005453:Fluorescence; D005609:Free Radicals; D005971:Glutamates / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006706:Homeostasis; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D005609:Free Radicals; D005971:Glutamates; D017470:Receptors, Glutamate; D002118:Calcium
Mekhanizmy destabilizatsii kal'tsievogo gomeostaza neĭrona pri giperstimuliatsii gliutamatnykh retseptorov.