Effect of the K+ Channel Modulations on Glutamate and K+ Concentrations in Rabbit Hippocampus during Transient Global Ischemia.
10.4097/kjae.1999.36.3.510
- Author:
Kyu Taek CHOI
1
;
Myung Won CHO
;
Byung Te SUH
;
Jeong Rak LEE
;
Hyung Seop PARK
;
Pan Dong RYU
Author Information
1. Department of Anesthesiology, University of Ulsan, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Ischemia, cerebral, Ion channel, K, Excitatory Aminoacids, glutamate
- MeSH:
Adenosine Triphosphate;
Animals;
Anoxia;
Brain;
Brain Ischemia;
Catheters;
Cerebrospinal Fluid;
Chromatography, Liquid;
Cromakalim;
Extracellular Space;
Glutamic Acid*;
Glyburide;
Halothane;
Hippocampus*;
Hypotension;
Inflation, Economic;
Ischemia*;
KATP Channels;
Microdialysis;
Microelectrodes;
Neck;
Neuroglia;
Neurons;
Neurotransmitter Agents;
Potassium;
Rabbits;
Reperfusion;
Tourniquets
- From:Korean Journal of Anesthesiology
1999;36(3):510-517
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Cerebral ischemia causes an increase in extracellular potassium ([K+]e) through activation of the KATP channel. This increase in [K+]e could result in neuronal depolarization and a reversal of the glutamate uptake system in glia. This may further contribute to the excessive concentrations of glutamate and asparate in the extracellular space during ischemia. If the early rise in [K+]e during ischemia could be attenuated, less excitotoxic neuronal damage may be the result. However, activation of KATP channels has been shown to attenuate the anoxia induced depolarization in the hippocampus and may reduce the release of excitatory neurotransmitters during cerebral ischemia. In this study, we address the question of whether KATP channel modulation affects [K+]e and whether it is related with extracellular glutamate concentrations. METHODS: After approval by the Animal Care and Use Committee, 18 New Zealand white rabbits were anesthetized with halothane and mechanically ventilated to maintain normocarbia. Microdialysis catheters were inserted into the left dorsal hippocampus and perfused with artificial cerebrospinal fluid at 2 ml/min. K+ sensitive microelectrodes were inserted into the contralateral hippocampus. A pneumatic tourniquet was placed loosely around the neck. Animals were randomized to receive glibenclamide (n=5, KATP blocker, 3.7 mg/kg) or cromakalim (n=5, KATP opener, 0.5 mg/kg). The control group (n=6) had neither drug. Ten-minute period of global cerebral ischemia was produced by inflation of the tourniquet combined with induced hypotension. Hippocampal [K+]e was measured throughout the periischemic period and glutamate concentrations in dialysate were determined by high-performance liquid chromatography. Peak levels were compared by ANOVA. RESULTS: Glutamate concentration significantly increased during ischemia period for all groups (p<0.05). In glibenclamide treated animals, brain glutamate concentration increased markedly during early reperfusion (t=I+15) compared to other groups (p<0.05). There were no statistical differences on ischemia-induced increases in [K+]e among the three groups. CONCLUSIONS: Although it was not possible to demonstrate an effect of modulators of the ATP sensitive K+ channel on [K+]e, glibenclamide increased glutamate during reperfusion. This paradoxical increase in glutamate after administration of a K+ channel blocker suggests that the mechanism of glutamate release is not related to [K+]e change.
