THE ROLE OF G-PROTEIN IN MUSCARINIC DEPOLARIZATION NEAR RESTING POTENTIAL IN CULTURED HIPPOCAMPAL-NEURONS

被引:18
作者
BROWN, LD
KIM, KM
NAKAJIMA, Y
NAKAJIMA, S
机构
[1] UNIV ILLINOIS, COLL MED, DEPT PHARMACOL, M-C 868, CHICAGO, IL 60612 USA
[2] UNIV ILLINOIS, COLL MED, DEPT ANAT & CELL BIOL, CHICAGO, IL 60612 USA
[3] PURDUE UNIV, DEPT BIOL SCI, W LAFAYETTE, IN 47907 USA
关键词
ACETYLCHOLINE; G-PROTEIN; MUSCARINIC RECEPTOR; PERTUSSIS TOXIN; HIPPOCAMPUS; CELL CULTURE;
D O I
10.1016/0006-8993(93)91661-B
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Cultured neurons from the CA1 and CA3 regions of the rat hippocampus were studied by using the whole-cell version of patch clamp. Application of acetylcholine (5-10 muM) or muscarine (20 muM) to a neuron with a holding potential of almost-equal-to -70 mV produced a slow inward current. This inward current was inhibited by atropine (1-2 muM). Loading the cell with GTPgammaS caused a change in the muscarinic response. In the control cells the muscarine-induced inward current recovered by 89%. On the other hand, in the GTPgammaS-loaded cells the inward current recovered by only 30%, indicating some irreversibility. Pertussis toxin treatment did not change the muscarine-induced slow inward current. Loading the cells with cyclic AMP (100 muM) plus IBMX (1 mM) (an inhibitor of phosphodiesterase) did not occlude the effect of muscarine. We conclude that the slow inward current is mediated through a pertussis toxin-insensitive G protein, and that cyclic AMP is not a part of the signal transduction cascade. The finding that the GTPgammaS-loaded cells did not show complete irreversibility was discussed in relation to the results of Benson et al. (J. Physiol., 404 (1988) 479-496), which showed that there are two ionic mechanisms responsible for the muscarine-induced depolarization. Occasionally cells were encountered, in which muscarine (or acetylcholine) evoked a large and rapid inward current, followed by the usual slow inward current. The time course of this rapid response was not affected by GTPgammaS.
引用
收藏
页码:200 / 209
页数:10
相关论文
共 45 条
[1]   CHOLINERGIC EXCITATION OF MAMMALIAN HIPPOCAMPAL PYRAMIDAL CELLS [J].
BENARDO, LS ;
PRINCE, DA .
BRAIN RESEARCH, 1982, 249 (02) :315-331
[2]   AN ANALYSIS OF THE DEPOLARIZATION PRODUCED IN GUINEA-PIG HIPPOCAMPUS BY CHOLINERGIC RECEPTOR STIMULATION [J].
BENSON, DM ;
BLITZER, RD ;
LANDAU, EM .
JOURNAL OF PHYSIOLOGY-LONDON, 1988, 404 :479-496
[3]   MUSCARINIC SUPPRESSION OF A NOVEL VOLTAGE-SENSITIVE K+ CURRENT IN A VERTEBRATE NEURON [J].
BROWN, DA ;
ADAMS, PR .
NATURE, 1980, 283 (5748) :673-676
[4]  
BROWN L D, 1988, Society for Neuroscience Abstracts, V14, P1328
[5]   MUSCARINIC AGONISTS BLOCK 5 DIFFERENT POTASSIUM CONDUCTANCES IN GUINEA-PIG SYMPATHETIC NEURONS [J].
CASSELL, JF ;
MCLACHLAN, EM .
BRITISH JOURNAL OF PHARMACOLOGY, 1987, 91 (02) :259-261
[6]   GABA CONDUCTANCE OF CHICK SPINAL-CORD AND DORSAL-ROOT GANGLION NEURONS IN CELL-CULTURE [J].
CHOI, DW ;
FISCHBACH, GD .
JOURNAL OF NEUROPHYSIOLOGY, 1981, 45 (04) :605-620
[7]   CHARACTERIZATION OF A SLOW CHOLINERGIC POST-SYNAPTIC POTENTIAL RECORDED INVITRO FROM RAT HIPPOCAMPAL PYRAMIDAL CELLS [J].
COLE, AE ;
NICOLL, RA .
JOURNAL OF PHYSIOLOGY-LONDON, 1984, 352 (JUL) :173-188
[8]   ALZHEIMERS-DISEASE - A DISORDER OF CORTICAL CHOLINERGIC INNERVATION [J].
COYLE, JT ;
PRICE, DL ;
DELONG, MR .
SCIENCE, 1983, 219 (4589) :1184-1190
[9]   THE EXCITATORY ACTION OF ACETYLCHOLINE ON HIPPOCAMPAL-NEURONS OF THE GUINEA-PIG AND RAT MAINTAINED INVITRO [J].
DODD, J ;
DINGLEDINE, R ;
KELLY, JS .
BRAIN RESEARCH, 1981, 207 (01) :109-127
[10]  
DUTAR P, 1988, J NEUROSCI, V8, P4214