In vivo elevation of extracellular potassium in the rat amygdala increases extracellular glutamate and aspartate and damages neurons.
It is well known that high potassium (K+) solutions introduced by microdialysis into normal brain increase the extracellular concentration of the excitatory amino acid glutamate, and in vitro studies suggest that a high exogenously applied glutamate concentration can produce excitotoxic neuronal death. However, only recently were in vivo studies undertaken to determine whether high-K+ exposure damages neurons. We implanted microdialysis probes into rat amygdalae bilaterally, and after a 2-h baseline period exposed one side to a modified Krebs-Ringer-bicarbonate solution containing 100 mmol/l KCl for 30,50 and 70 min, followed by a 2-h recovery period, and 70 min and 3 h without a recovery period. Of 100.9 +/- 2.0 mmol/l KCl, 12.0 +/- 1.0% was extracted by amygdalar tissue in vivo. Election of the extracellular K+ concentration in the amygdala for 70 min or longer without a recovery period produced extensive neuronal damage and edematous-appearing neuropil in the tissue dialysed, as well as loss of normal neurons. Histological evidence of edema subsided in the groups with a 2-h recovery period. Although the number of damaged neurons was not significantly higher in the group with a 70 min high-K+ exposure and 2-h recovery period, the number of normal neurons was reduced, suggesting cell loss. During 70-min high-K+ exposure, the extracellular glutamate concentration increased to 242-377% of baseline during the first 60 min, and extracellular aspartate rose to 162-213% during the first 50 min; extracellular taurine rose even higher, to 316-567% of baseline, and glutamine fell to 14-27% of baseline. Extracellular serine was decreased at 20, 50 and 70 min of high-K+ exposure; extracellular glycine was unchanged. The elevated extracellular glutamate and aspartate concentrations suggest that exposure of the amygdala to high extracellular K+ may produce cell death through an excitotoxic process, and point the way to future studies to define the specific mechanisms involved.
Fujikawa
D G
DG
Experimental Neurology Laboratory, Sepulveda VA Medical Center, CA 91343, USA.
Kim
J S
JS
Daniels
A H
AH
Alcaraz
A F
AF
Sohn
T B
TB
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D001929:Brain Edema; D005110:Extracellular Space / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007700:Kinetics; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D011188:Potassium / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000378:metabolism; D013654:Taurine / Q000378:metabolism
D005973:Glutamine; D013654:Taurine; D001224:Aspartic Acid; D018698:Glutamic Acid; D012694:Serine; D011189:Potassium Chloride; D011188:Potassium; D005998:Glycine