Inorganic Polyphosphate Regulates AMPA and NMDA Receptors and Protects Against Glutamate Excitotoxicity via Activation of P2Y Receptors
Maiolino M., O'Neill N., Lariccia V., Amoroso S., Sylantyev S., Shtro P. R., Abramov A. Y.
Journal of Neuroscience
Vol.39, Issue31, P. 6038-6048
Опубликовано: 2019
Тип ресурса: Статья
DOI:10.1523/JNEUROSCI.0314-19.2019
Аннотация:
Glutamate is one of the most important neurotransmitters in the process of signal transduction in the CNS. Excessive amounts of this neurotransmitter lead to glutamate excitotoxicity, which is accountable for neuronal death in acute neurological disorders, including stroke and trauma, and in neurodegenerative diseases. Inorganic polyphosphate (PolyP) plays multiple roles in the mammalian brain, including function as a calcium-dependent gliotransmitter mediating communication between astrocytes, while its role in the regulation of neuronal activity is unknown. Here we studied the effect of PolyP on glutamate-induced calcium signal in primary rat neurons in both physiological and pathological conditions. We found that preincubation of primary neurons with PolyP reduced glutamate-induced and AMPA-induced but not the NMDA-induced calcium signal. However, in rat hippocampal acute slices, PolyP reduced ion flux through NMDA and AMPA receptors in native neurons. The effect of PolyP on glutama
Ключевые слова:
AMPA; excitotoxicity; glutamate; inorganic polyphosphate; neuron; NMDA
AMPA receptor; glutamic acid; n methyl dextro aspartic acid receptor; polyphosphate; purinergic P2Y1 receptor; animal; calcium signaling; cell culture; drug effect; female; male; metabolism; nerve cell; physiology; rat; Sprague Dawley rat; Animals; Calcium Signaling; Cells, Cultured; Female; Glutamic Acid; Male; Neurons; Polyphosphates; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Receptors, Purinergic P2Y1
Язык текста: Английский
ISSN: 1529-2401
Maiolino M.
O'Neill N.
Lariccia V.
Amoroso S.
Sylantyev S.
Shtro P. R. Plamena Rumyanova 1977-
Abramov A. Y.
Маиолино М.
О'Неилл Н.
Лариccиа В.
Аморосо С.
Сyлантьев С.
Штро П. Р. Пламена Румянова 1977-
Абрамов А. Y.
Inorganic Polyphosphate Regulates AMPA and NMDA Receptors and Protects Against Glutamate Excitotoxicity via Activation of P2Y Receptors
Текст визуальный непосредственный
Journal of Neuroscience
Society for Neuroscience
Vol.39, Issue31 P. 6038-6048
2019
Статья
AMPA excitotoxicity glutamate inorganic polyphosphate neuron NMDA
AMPA receptor glutamic acid n methyl dextro aspartic acid receptor polyphosphate purinergic P2Y1 receptor animal calcium signaling cell culture drug effect female male metabolism nerve cell physiology rat Sprague Dawley rat Animals Calcium Signaling Cells, Cultured Female Glutamic Acid Male Neurons Polyphosphates Rats Rats, Sprague-Dawley Receptors, AMPA Receptors, N-Methyl-D-Aspartate Receptors, Purinergic P2Y1
Glutamate is one of the most important neurotransmitters in the process of signal transduction in the CNS. Excessive amounts of this neurotransmitter lead to glutamate excitotoxicity, which is accountable for neuronal death in acute neurological disorders, including stroke and trauma, and in neurodegenerative diseases. Inorganic polyphosphate (PolyP) plays multiple roles in the mammalian brain, including function as a calcium-dependent gliotransmitter mediating communication between astrocytes, while its role in the regulation of neuronal activity is unknown. Here we studied the effect of PolyP on glutamate-induced calcium signal in primary rat neurons in both physiological and pathological conditions. We found that preincubation of primary neurons with PolyP reduced glutamate-induced and AMPA-induced but not the NMDA-induced calcium signal. However, in rat hippocampal acute slices, PolyP reduced ion flux through NMDA and AMPA receptors in native neurons. The effect of PolyP on glutama