Cr. Rose et al., EFFECTS OF GLUCOSE DEPRIVATION, CHEMICAL HYPOXIA, AND SIMULATED ISCHEMIA ON NA-CORD ASTROCYTES( HOMEOSTASIS IN RAT SPINAL), The Journal of neuroscience, 18(10), 1998, pp. 3554-3562
A steep inwardly directed Na+ gradient is essential for glial function
s such as glutamate reuptake and regulation of intracellular ion conce
ntrations, We investigated the effects of glucose deprivation, chemica
l hypoxia, and simulated ischemia on intracellular Na+ concentration (
[Na+](i)) in cultured spinal cord astrocytes using fluorescence ratio
imaging with sodium binding benzofuran isophthalate (SBFI) AM. Glucose
removal or chemical hypoxia (induced by 10 mM NaN3) for 60 min increa
sed [Na+](i) from a baseline of 8.3 to 11 mM. Combined glycolytic and
respiratory blockage by NaN3 and 0 glucose saline caused [Na+](i) to i
ncrease by 20 mM, similar to the [Na+](i) increases elicited by blocki
ng the Na+/K+-ATPase with ouabain. Recovery from large [Na+](i) increa
ses (>15 mM) induced by the glutamatergic agonist kainate was attenuat
ed during glucose deprivation or NaN3 application and was blocked in N
aN3 and 0 glucose. To mimic in vivo ischemia, we exposed astrocytes to
NaN3 and 0 glucose saline containing L-lactate and glutamate with inc
reased [K+] and decreased [Na+], [Ca2+], and pH. This induced an [Na+]
(i) decrease followed by an [Na+](i) rise and a further [Na+](i) incre
ase after reperfusion with standard saline, Similar multiphasic [Na+](
i) changes were observed after NaN3 and 0 glucose saline with only red
uced [Na+](e). Our results suggest that the ability to maintain a low
[Na+](i) enables spinal cord astrocytes to continue uptake of K+ and/o
r glutamate at the onset of energy failure. With prolonged energy fail
ure, however, astrocytic [Na+](i) rises with loss of their steep trans
membrane Na+ gradient, astrocytes may aggravate metabolic insults by c
arrier reversal and release of acid, K+, and/or glutamate into the ext
racellular space.