THE CALCIUM RESPONSE TO THE EXCITOTOXIN KAINATE IS AMPLIFIED BY SUBSEQUENT REDUCTION OF EXTRACELLULAR-SODIUM

: COURTNEY MJ, ENKVIST MOK, AKERMAN KEO

Publisher: PERGAMON-ELSEVIER SCIENCE LTD

: 1995

: Neuroscience

: NEUROSCIENCE

: 68

: 4

: 1051

: 1057

: 7

: 0306-4522

DOI: https://doi.org/10.1016/0306-4522(95)00211-Z

The relation between intracellular and extracellular [Na+] and [Ca2+] and membrane potential during stimulation of non-N-methyl-D-aspartate glutamate receptors has been studied in cerebellar granule cells using the fluorescent indicators SBFI, fura-2 and the bisoxonol membrane potential probe DiBaC(4)(3). Kainate increased both [Ca2+](i) (intracellular [Ca2+]) and [Na+](i) (intracellular [Na+]) and depolarized the membrane. This elevation of [Ca2+](i) was only partially dependent on the presence of extracellular Na+ at the time of kainate addition. Removal of extracellular Na+ itself had a very minor effect on the [Ca2+](i) or membrane potential of unstimulated cells. If extracellular Na+ was removed (in order to reverse the [Na+] gradient) or its concentration reduced during stimulation with kainate, the membrane depolarization recovered as expected. However, the intracellular level of sodium recovered only very slowly and the [Ca2+](i) rose sharply, rather than recovering as might be expected on repolarization of depolarized cells possessing voltage sensitive calcium channels. This effect of extracellular [Na+] reduction on [Ca2+](i) was mimicked by ouabain, another agent that causes accumulation of [Na+] in cells.These results suggest that Na+/Ca2+ exchange may play a major role in calcium homeostasis in stimulated cells, and that the levels of Na+ inside and outside the cell are critical in determining the effect of receptor stimulation on the intracellular [Ca2+].