Pe. Bickler et Bm. Hansen, CAUSES OF CALCIUM-ACCUMULATION IN RAT CORTICAL BRAIN-SLICES DURING HYPOXIA AND ISCHEMIA - ROLE OF ION CHANNELS AND MEMBRANE DAMAGE, Brain research, 665(2), 1994, pp. 269-276
To better understand why neurons accumulate calcium during cerebral is
chemia, the influence of specific ion channel inhibitors on the rise i
n cytosolic free calcium ([Ca2+](c)) during hypoxia or ischemia was ev
aluated in rat cerebrocortical brain slices. [Ca2i](c) was measured fl
uorometrically with the dye fura-2 during hypoxia (95% N-2/5% CO, or 1
00 mu M NaCN), simulated ischemia (100 mu M NaCN plus 3.5 mM iodoaceta
te), or 0.5-1.0 mM glutamate. Hypoxia or ischemia increased [Ca+2](c)
from 100-250 nM to 1,000-2,500 nM within 3-5 min. Greater than 85% of
the calcium accumulation was influx from the extracellular medium. The
non-competitive N-methyl-D-aspartate (NMDA) inhibitor MK-801 reduced
[Ca2+](c) accumulation during hypoxia, but antagonism of alpha-amino-3
-hydroxy-5-methyl-4-isoxazole (AMPA) receptors or voltage-gated sodium
or calcium channels or Na+/Ca2+ exchangers had no effect. During isch
emia, combined antagonism of NMDA, AMPA and voltage-gated sodium chann
els slowed the rate of calcium accumulation, but not concentration at
5 min. Membrane damage, as indicated by leakage of lactate dehydrogena
se into superfusate, occurred coincidentally with calcium influx and A
TP loss during both hypoxia and ischemia. We conclude that cytosolic c
alcium changes during hypoxia or ischemia in cortical brain slices are
due to multiple mechanisms, are incompletely inhibited by combined io
n channel blockade, and are associated with disruption of cell membran
e integrity.