CAUSES OF CALCIUM-ACCUMULATION IN RAT CORTICAL BRAIN-SLICES DURING HYPOXIA AND ISCHEMIA - ROLE OF ION CHANNELS AND MEMBRANE DAMAGE

Citation
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
Citations number
28
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
00068993
Volume
665
Issue
2
Year of publication
1994
Pages
269 - 276
Database
ISI
SICI code
0006-8993(1994)665:2<269:COCIRC>2.0.ZU;2-P
Abstract
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.