DIFFERENTIAL-EFFECTS OF GABAERGIC LIGANDS IN MOUSE AND RAT HIPPOCAMPAL-NEURONS

被引:33
作者
AGUAYO, LG [1 ]
PANCETTI, FC [1 ]
KLEIN, RL [1 ]
HARRIS, RA [1 ]
机构
[1] UNIV COLORADO, HLTH SCI CTR, DEPT PHARMACOL, DENVER, CO 80262 USA
关键词
GABA(A) RECEPTOR; BENZODIAZEPINE; CL-; CURRENT; HIPPOCAMPAL NEURON; PENTOBARBITAL; ETHANOL; CL-218,872;
D O I
10.1016/0006-8993(94)91403-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Previous electrophysiological studies suggested that GABA(A) receptors in rat hippocampal neurons might be less sensitive to ethanol than mouse neurons. Therefore, we examined the effects of ethanol (0.5-850 mM) in cultured mouse (C57BL/6) and rat (Sprague-Dawley) neurons. In 35% of the mouse neurons, the Cl- current was potentiated by ethanol starting at 0.5 mM. In all of the rat neurons examined, on the other hand, the current was potentiated by concentrations starting at 200 mM. We also studied the effects of GABA and other GABAergic ligands. GABA(A) receptors in rat and mouse neurons displayed EC(50)s for GABA of 9 +/- 0.3 and 17 +/- 0.8 mu M, respectively and ethanol did not significantly change these values. The EC(50) for diazepam was 92 +/- 3 and 120 +/- 8 nM in rat and mouse, respectively. Pentobarbital enhanced the current with EC(50)s of 84 +/- 3 and 106 +/- 6 mu M in rat and mouse, respectively. The sensitivity for Cl-218,872, which binds preferentially to the Type I benzodiazepine receptor, was similar in all the neurons. RO 15-4513, an inverse partial agonist to the benzodiazepine receptor, was not effective in reversing the potentiation of the Cl- current in rat neurons and only slightly reduced the potentiation in mouse neurons. The receptors in rat neurons were more sensitive to external Zn2+; the current was inhibited by 50% with a concentration of 93 +/- 3 and 244 +/- 9 mu M in rat and mouse, respectively. Analysis of mRNA encoding for the gamma 2L receptor subunit showed similar levels in rat and mouse neurons. The data suggest that most pharmacological properties of hippocampal GABA(A) mouse and rat receptors are comparable, with the exception of the sensitivity to ethanol and Zn2+. These differences can not be explained by differential expression of gamma 2L subunits. We provide good experimental evidence indicating a difference in the sensitivity of the GABA(A) receptor to GABAergic ligands in two distinct animal species.
引用
收藏
页码:97 / 105
页数:9
相关论文
共 40 条
  • [11] PROLONGATION OF INHIBITORY POSTSYNAPTIC CURRENTS BY PENTOBARBITAL, HALOTHANE AND KETAMINE IN CA1 PYRAMIDAL CELLS IN RAT HIPPOCAMPUS
    GAGE, PW
    ROBERTSON, B
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1985, 85 (03) : 675 - 681
  • [12] IMPROVED PATCH-CLAMP TECHNIQUES FOR HIGH-RESOLUTION CURRENT RECORDING FROM CELLS AND CELL-FREE MEMBRANE PATCHES
    HAMILL, OP
    MARTY, A
    NEHER, E
    SAKMANN, B
    SIGWORTH, FJ
    [J]. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1981, 391 (02): : 85 - 100
  • [13] CENTRAL NERVOUS-SYSTEM EFFECTS OF THE IMIDAZODIAZEPINE RO-15-4513
    HARRIS, CM
    LAL, H
    [J]. DRUG DEVELOPMENT RESEARCH, 1988, 13 (04) : 187 - 203
  • [14] LEGENDRE P, 1991, MOL PHARMACOL, V39, P267
  • [15] STRUCTURAL AND FUNCTIONAL BASIS FOR GABAA RECEPTOR HETEROGENEITY
    LEVITAN, ES
    SCHOFIELD, PR
    BURT, DR
    RHEE, LM
    WISDEN, W
    KOHLER, M
    FUJITA, N
    RODRIGUEZ, HF
    STEPHENSON, A
    DARLISON, MG
    BARNARD, EA
    SEEBURG, PH
    [J]. NATURE, 1988, 335 (6185) : 76 - 79
  • [16] CEREBELLAR GABA-A RECEPTOR SELECTIVE FOR A BEHAVIORAL ALCOHOL ANTAGONIST
    LUDDENS, H
    PRITCHETT, DB
    KOHLER, M
    KILLISCH, I
    KEINANEN, K
    MONYER, H
    SPRENGEL, R
    SEEBURG, PH
    [J]. NATURE, 1990, 346 (6285) : 648 - 651
  • [17] ANTAGONISM OF ETHANOL EFFECTS BY RO 15-4513 - AN ELECTROPHYSIOLOGICAL ANALYSIS
    MARROSU, F
    CARCANGIU, G
    PASSINO, N
    ARAMO, S
    MEREU, G
    [J]. SYNAPSE, 1989, 3 (02) : 117 - 128
  • [18] MEHTA AK, 1988, J PHARMACOL EXP THER, V246, P558
  • [19] POTENTIATION OF GAMMA-AMINOBUTYRIC ACID-MEDIATED CHLORIDE FLUX BY PENTOBARBITAL AND DIAZEPAM BUT NOT ETHANOL
    MIHIC, SJ
    WU, PH
    KALANT, H
    [J]. JOURNAL OF NEUROCHEMISTRY, 1992, 58 (02) : 745 - 751
  • [20] MOLECULAR-BIOLOGY OF GABA-A RECEPTORS
    OLSEN, RW
    TOBIN, AJ
    [J]. FASEB JOURNAL, 1990, 4 (05) : 1469 - 1480