Effects of K+ channel modulators on extracellular K+ accumulation during ischemia in the rat hippocampal slice.
- Author:
Jin Kyu CHOI
1
;
Boe Gwun CHUN
;
Pan Dong RYU
Author Information
1. Department of Pharmacology, College of Veterinary Medicine, Seoul National University, Suwon 441-744, South Korea.
- Publication Type:Original Article
- Keywords:
Ischemia;
Extracellular K+;
Population spike;
Hippocampal slice;
K+ channel;
4-aminopyridine;
NS-1619;
Tetraethylammonium;
Glibenclamide
- MeSH:
4-Aminopyridine;
Animals;
Brain;
Brain Ischemia;
Glyburide;
Hip;
Ischemia*;
Niflumic Acid;
Pinacidil;
Rats*;
Synaptic Transmission;
Tetraethylammonium;
Tolbutamide
- From:The Korean Journal of Physiology and Pharmacology
1997;1(6):681-690
- CountryRepublic of Korea
- Language:English
-
Abstract:
Loss of synaptic transmission and accumulation of extracellular K+((K+)o) are the key features in ischemic brain damage. Here, we examined the effects of several K+ channel modulators on the early ischemic changes in population spike (PS) and (K+)o in the CA1 pyramidal layer of the rat hippocampal slice using electrophysiological techniques. After onset of anoxic aglycemia (AA), orthodromic field potentials decreased and disappeared in 3.3 +/- 0.22 min (mean +/- SEM, n = 40). The hypoxic injury potential (HIP), a transient recovery of PS appeared at 6.0 +/- 0.25 min (n = 40) in most slices during AA and lasted for 3.3 +/- 0.43 min. (K+)o increased initially at a rate of 0.43 mM/min (Phase 1) and later at a much faster rate (12.45 mM/min, Phase 2). The beginning of Phase 2 was invariably coincided with the disappearance of HIP. Among K+ channel modulators tested such as 4-aminopyridine (0.03, 0.3 mM), tetraethylammonium (0.1 mM), NS1619 (0.3 ~ 10 muM), niflumic acid (0.1 mM), glibenclamide (40 muM), tolbutamide (300 muM) and pinacidil (100 muM), only 4-aminopyridine (0.3 mM) induced slight increase of (K+)o during Phase 1. However, none of the above agents modulated the pattern of Phase 2 in (K+)o in response to AA. Taken together, the experimental data suggest that 4-aminopyridine-sensitive K+ channels, large conductance Ca2+/-activated K+ channels and ATP-sensitive K+ channels may not be the major contributors to the sudden increase of (K+)o during the early stage of brain ischemia, suggesting the presence of other routes of K+ efflux during brain ischemia.
