ATP receptor-mediated enhancement of fast excitatory neurotransmitter release in the brain

被引:120
作者
Khakh, BS [1 ]
Henderson, G [1 ]
机构
[1] Univ Bristol, Sch Med Sci, Dept Pharmacol, Bristol BS8 1TD, Avon, England
关键词
D O I
10.1124/mol.54.2.372
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
ATP-gated cation channels (P2X receptors) exist on the soma of proprioceptive neurons in the trigeminal mesencephalic nucleus (MNV) in the brain stem. However, these pseudomonopolar neurons seem to receive no synaptic input to their soma; we therefore hypothesized that in MNV neurons, the P2X receptors of importance may be those located on their central terminal projections. Here, we show in trigeminal mesencephalic motor nucleus neurons, which receive their major input from the MNV, that both exogenous ATP (1 mM) and high frequency focal stimulation to evoke endogenous ATP release enhanced the frequency of spontaneous fast excitatory postsynaptic currents (EPSCs) with no change in their amplitude. The enhancement was reduced by the antagonists suramin (300 mu M) and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (30 mu M) and persisted when action potential conduction was blocked with tetrodotoxin (1 mu M). Thus, functional P2X receptors are expressed on nerve terminals in the brain stem, where they increase the spontaneous release of glutamate onto trigeminal mesencephalic motor nucleus neurons.
引用
收藏
页码:372 / 378
页数:7
相关论文
共 38 条
[1]  
ALLAGIER C, 1995, N-S ARCH PHARMACOL, V352, P17
[2]  
Bardoni R, 1997, J NEUROSCI, V17, P5297
[3]  
BURNSTOCK G, 1972, PHARMACOL REV, V24, P509
[4]  
Burnstock G, 1996, CIBA F SYMP, V198, P1
[5]   Regulation of glutamate release by presynaptic kainate receptors in the hippocampus [J].
Chittajallu, R ;
Vignes, M ;
Dev, KK ;
Barnes, JM ;
Collingridge, GL ;
Henley, JM .
NATURE, 1996, 379 (6560) :78-81
[6]   A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission [J].
Clarke, VRJ ;
Ballyk, BA ;
Hoo, KH ;
Mandelzys, A ;
Pellizzari, A ;
Bath, CP ;
Thomas, J ;
Sharpe, EF ;
Davies, CH ;
Ornstein, PL ;
Schoepp, DD ;
Kamboj, RK ;
Collingridge, GL ;
Lodge, D ;
Bleakman, D .
NATURE, 1997, 389 (6651) :599-603
[7]  
Collo G, 1996, J NEUROSCI, V16, P2495
[8]   Distinct ATP receptors on pain-sensing and stretch-sensing neurons [J].
Cook, SP ;
Vulchanova, L ;
Hargreaves, KM ;
Elde, R ;
McCleskey, EW .
NATURE, 1997, 387 (6632) :505-508
[9]   Primary- and secondary-like jaw-muscle spindle afferents have characteristic topographic distributions [J].
Dessem, D ;
Donga, R ;
Luo, PF .
JOURNAL OF NEUROPHYSIOLOGY, 1997, 77 (06) :2925-2944
[10]   ATP RECEPTOR-MEDIATED SYNAPTIC CURRENTS IN THE CENTRAL-NERVOUS-SYSTEM [J].
EDWARDS, FA ;
GIBB, AJ ;
COLQUHOUN, D .
NATURE, 1992, 359 (6391) :144-147