Mj. Courtney et al., THE CALCIUM RESPONSE TO THE EXCITOTOXIN KAINATE IS AMPLIFIED BY SUBSEQUENT REDUCTION OF EXTRACELLULAR-SODIUM, Neuroscience, 68(4), 1995, pp. 1051-1057
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 po
tential probe DiBaC(4)(3). Kainate increased both [Ca2+](i) (intracell
ular [Ca2+]) and [Na+](i) (intracellular [Na+]) and depolarized the me
mbrane. This elevation of [Ca2+](i) was only partially dependent on th
e presence of extracellular Na+ at the time of kainate addition. Remov
al of extracellular Na+ itself had a very minor effect on the [Ca2+](i
) or membrane potential of unstimulated cells. If extracellular Na+ wa
s removed (in order to reverse the [Na+] gradient) or its concentratio
n reduced during stimulation with kainate, the membrane depolarization
recovered as expected. However, the intracellular level of sodium rec
overed only very slowly and the [Ca2+](i) rose sharply, rather than re
covering as might be expected on repolarization of depolarized cells p
ossessing voltage sensitive calcium channels. This effect of extracell
ular [Na+] reduction on [Ca2+](i) was mimicked by ouabain, another age
nt that causes accumulation of [Na+] in cells. These results suggest t
hat Na+/Ca2+ exchange may play a major role in calcium homeostasis in
stimulated cells, and that the levels of Na+ inside and outside the ce
ll are critical in determining the effect of receptor stimulation on t
he intracellular [Ca2+].