Non-GABAergic effects of midazolam, diazepam and flumazenil on voltage-dependent ion currents in NG108-15 cells

被引:34
作者
Ishizawa, Y [1 ]
Furuya, K [1 ]
Yamagishi, S [1 ]
Dohi, S [1 ]
机构
[1] NATL INST PHYSIOL SCI,DEPT CELL PHYSIOL,OKAZAKI,AICHI 444,JAPAN
关键词
benzodiazepines; diazepam; electrophysiology; flumazenil; midazolam; NG108-15; patch-clamp; voltage-dependent ion currents;
D O I
10.1097/00001756-199707280-00042
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
NON-gamma-AMINOBUTYRIC acid (GABA)-mediated effects of benzodiazepines (BZs) have not been widely investigated. However, there is significant evidence in the literature to suggest that several experimental and clinical observations are inconsistent with the commonly accepted GABAergic mechanisms of action for these drugs. The purpose of the present study was to explore electrophysiological effects of midazolam, diazepam and a specific BZ antagonist, flumazenil, using patch-clamp techniques in NG108-15 cells which do not express the GABA(A) receptor. Midazolam and diazepam decreased Na+, K+ and Ca2+ currents in a dose-related manner. Ca2+ currents were reduced more significantly by diazepam than by midazolam. Flumazenil showed no effects on voltage-dependent ion currents. GABA by itself showed neither effects on the membrane potential nor these ion currents. Midazolam and diazepam, but not flumazenil, exhibited effects on voltage-dependent ion currents in cultured neurons.
引用
收藏
页码:2635 / 2638
页数:4
相关论文
共 19 条
[1]
MICROMOLAR AFFINITY BENZODIAZEPINE RECEPTORS - IDENTIFICATION AND CHARACTERIZATION IN CENTRAL NERVOUS-SYSTEM [J].
BOWLING, AC ;
DELORENZO, RJ .
SCIENCE, 1982, 216 (4551) :1247-1250
[2]
LOW-DOSE BENZODIAZEPINE NEURONAL INHIBITION - ENHANCED CA-2+-MEDIATED K+-CONDUCTANCE [J].
CARLEN, PL ;
GUREVICH, N ;
POLC, P .
BRAIN RESEARCH, 1983, 271 (02) :358-364
[3]
ENHANCED NEURONAL K+ CONDUCTANCE - A POSSIBLE COMMON MECHANISM FOR SEDATIVE-HYPNOTIC DRUG-ACTION [J].
CARLEN, PL ;
GUREVICH, N ;
DAVIES, MF ;
BLAXTER, TJ ;
OBEIRNE, M .
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 1985, 63 (07) :831-837
[4]
THE EXCITATORY EFFECTS OF THE SPECIFIC BENZODIAZEPINE ANTAGONIST RO14-7437, MEASURED INTRACELLULARLY IN HIPPOCAMPAL CA1 CELLS [J].
CARLEN, PL ;
GUREVICH, N ;
POLC, P .
BRAIN RESEARCH, 1983, 271 (01) :115-119
[5]
DEVELOPMENTAL TIME COURSES OF NA AND CA SPIKES IN NEURO-BLASTOMA X GLIOMA HYBRID-CELLS [J].
FURUYA, K ;
FURUYA, S ;
YAMAGISHI, S .
DEVELOPMENTAL BRAIN RESEARCH, 1983, 11 (02) :229-234
[6]
GARNER CR, 1988, PROG NEUROBIOL, V63, P831
[7]
IMPROVED PATCH-CLAMP TECHNIQUES FOR HIGH-RESOLUTION CURRENT RECORDING FROM CELLS AND CELL-FREE MEMBRANE PATCHES [J].
HAMILL, OP ;
MARTY, A ;
NEHER, E ;
SAKMANN, B ;
SIGWORTH, FJ .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1981, 391 (02) :85-100
[8]
NEUROPHARMACOLOGY OF CULTURED-CELLS - STUDIES ON RECEPTORS, SYNAPSES AND NEURONAL FUNCTION OF CLONAL CELLS [J].
HIGASHIDA, H ;
MIKI, N .
FOLIA PHARMACOLOGICA JAPONICA, 1981, 77 (02) :99-113
[9]
HIGASHIDA H, 1992, BIOCHEMISTRY-US, V64, P219
[10]
*HOSP PAT STUDY GR, 1992, CLIN THER, V14, P924