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The role of intracellular Na + and mitochondria in buffering of kainate‐induced intracellular free Ca 2+ changes in rat forebrain neurones
Author(s) -
Hoyt Kari R.,
Stout Amy K.,
Cardman Jamie M.,
Reynolds Ian J.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.103bo.x
Subject(s) - kainate receptor , forebrain , glutamate receptor , nmda receptor , mitochondrion , stimulation , biophysics , intracellular , biology , membrane potential , kainic acid , receptor , chemistry , medicine , endocrinology , biochemistry , ampa receptor , central nervous system
1 We have examined the mechanisms by which cultured central neurones from embryonic rat brain buffer intracellular Ca 2+ loads following kainate receptor activation using fluorescent indicators of [Ca 2+ ] i and [Na + ] i . 2 Stimulation of cultured forebrain neurones with 100 μ m kainate produced a rapid increase in [Ca 2+ ] i that displayed a variable rate of recovery. Kainate also increased [Na + ] i with a response that was slightly slower in onset and markedly slower in recovery. 3 The recovery of [Ca 2+ ] i to baseline was not very sensitive to the [Na + ] i . The magnitude of the increase in [Na + ] i in response to kainate did not correlate well with the [Ca 2+ ] i recovery time, and experimental manipulations that altered [Na + ] i did not have a large impact on the rate of recovery of [Ca 2+ ] i . 4 The recovery of [Ca 2+ ] i to baseline was accelerated by the mitochondrial Na + ‐Ca 2+ exchange inhibitor CGP‐37157, suggesting that the recovery rate is influenced by release of Ca 2+ from a mitochondrial pool and also that variation in the recovery rate is related to the extent of mitochondrial Ca 2+ loading. Kainate did not alter the mitochondrial membrane potential. 5 These studies reveal that mitochondria have a central role in buffering neuronal [Ca 2+ ] i changes mediated by non‐ N ‐methyl‐D‐aspartate (NMDA) glutamate receptors, and that the variation in recovery times following kainate receptor activation reflects a variable degree of mitochondrial Ca 2+ loading. However, unlike NMDA receptor‐mediated Ca 2+ loads, kainate receptor activation has minimal effects on mitochondrial function.