해마절편의 허혈성 K+ 축적에 대한 K+채널 조절 약물의 작용

• 영문명: Effects of K+ Channel Modulators on Extracellular K+ Accumulation during Ischemia in the Rat Hippocampal Slice
• 발행기관: 대한생리학회-대한약리학회
• 저자명: 최진규(Jin Kyu Choi) 전보권(Boe Gwun Chun) 류판동(Pan Dong Ryu)
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제1권 제6호, 681~690쪽, 전체 10쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 1997.01.01

영문 초록

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 ՌM), niflumic acid (0.1 mM), glibenclamide (40 ՌM), tolbutamide (300 ՌM) and pinacidil (100 ՌM), 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 Ca^2⁢-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.

키워드

Ischemia Extracellular K^⁢ Population spike Hippocampal slice K^⁢ channel 4-aminopyridine NS-1619 Tetraethylammonium Glibenclamide