Role of protein kinase C in Ca(2+) homeostasis disorders in cultured rat neurons during hyperstimulation of glutamate receptors.
The primary culture of rat cerebellar neurons was used to study protein kinase C activity, intracellular variations in calcium concentration ([Ca(2+)]i), changes in the mitochondrial potential, and neuronal death during hyperstimulation of glutamate receptors and after 24-h incubation with phorbol ester. Prolonged exposure of neurons to glutamate (100 microM, 45 min) was followed by the development of delayed calcium dysregulation. Protein kinase C activity depended on the time of cell incubation with glutamate. Protein kinase C activity increased in response to application of glutamate for 15 min. However, protein kinase C activity decreased after 45-min exposure to glutamate and development of delayed calcium dysregulation. Protein kinase C activity was nearly undetected after 24-h preincubation of neurons with phorbol ester. Under these conditions, delayed calcium dysregulation developed more slowly and was observed in a smaller number of neurons. Neuronal death decreased to 2+/-1%. Our results suggest that protein kinase C plays an important role in death of neurons, which exhibit delayed calcium dysregulation during glutamate treatment.
Persiyantseva
N A
NA
Laboratory of Membranology, Research Center of Child Health, Russian Academy of Medical Sciences, Moscow, Russia. nadushka99@rambler.ru
Birikh
K R
KR
Dvoretskova
E A
EA
Pinelis
V G
VG
Khodorov
B I
BI
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000494:pharmacology; D006706:Homeostasis; D053078:Membrane Potential, Mitochondrial; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium