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Short‐term block of Na + /K + ‐ATPase in neuro‐glial cell cultures of cerebellum induces glutamate dependent damage of granule cells
Author(s) -
Stelmashook E.V.,
Weih M.,
Zorov D.,
Victorov I.,
Dirnagl U.,
Isaev N.
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)00922-9
Subject(s) - glutamate receptor , cerebellum , ouabain , nmda receptor , granule (geology) , neuroglia , depolarization , biology , membrane potential , receptor , mitochondrion , microbiology and biotechnology , biophysics , biochemistry , chemistry , endocrinology , central nervous system , sodium , paleontology , organic chemistry
Granule cells in a dissociated neuro‐glial cell culture of cerebellum when exposed to ouabain (10 −3 M) for 25 min apparently swell, increase their [Ca 2+ ] i with obvious depolarization of the mitochondrial membrane. In 3 h after ouabain was omitted from the solution, 62±3% of granule cells had pycnotic nuclei. The supplement of a solution with competitive specific antagonist of NMDA receptors, L ‐2‐amino‐7‐phosphonoheptanoate (10 −4 M, APH) together with ouabain prevented cells from swelling, mitochondrial deenergization, neuronal death and increase of [Ca 2+ ] i . These data suggest that cellular Na + /K + ‐ATPase inactivation in neuro‐glial cell cultures of cerebellum leads to glutamate (Glu) accumulation, hyperstimulation of glutamate receptors, higher Ca 2+ and Na + influxes into the cells through the channels activated by Glu. This process leads to cell swelling, mitochondrial deenergization and death of granule cells. Possibly, the decrease of Na + /K + ‐ATPase activity in brain cells can lead to the onset of at least some chronic neurological disorders.