ACTIVATION OF SPECIFIC ATP RECEPTORS INDUCES A RAPID INCREASE IN INTRACELLULAR CALCIUM-IONS IN RAT HYPOTHALAMIC NEURONS

被引:59
作者
CHEN, ZP
LEVY, A
LIGHTMAN, SL
机构
[1] Department of Medicine, University of Bristol, Bristol, BS2 8HW, Marlborough Street
关键词
EXTRACELLULAR ATP; CYTOSOLIC CA-2+; CULTURED HYPOTHALAMIC NEURON;
D O I
10.1016/0006-8993(94)90151-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We have used real-time dynamic video imaging of Fura-2 fluorescence to study the acute effects of external ATP on [Ca2+]i in cultured rat hypothalamic neurons. The addition of ATP at muM concentrations, but not adenosine, AMP, ADP or GTP, produced a rapid, dose-dependent increase in cytosolic Ca2+. The hydrolysis-resistant ATP analogues 3-thio-ATP and beta,gamma-imido-ATP produced a similar response but alpha,beta-methylene ATP had much lower efficacy. The ATP response was inhibited by 10 muM nifedipine, abolished by 50 muM cadmium and by the absence of extracellular Ca2+, but was unaffected by ryanodine or omega-conotoxin GVIA. The P2-purinoceptor antagonist suramin reversibly and selectively inhibited the ATP response but had no effect on other neurotransmitter-induced Ca(i)2+ responses. Antagonists to muscarinic, nicotinic, NMDA, non-NMDA, GABA, 5-HT and adenosine receptors had no effect on the ATP response. Thus the Ca2+ response of hypothalamic neurons to ATP is mediated by specific suramin-sensitive ATP-receptors, activation of which is independent of ATP hydrolysis and results in an influx of extracellular Ca2+ largely through high voltage-gated Ca2+ channels. These findings support the assertion that ATP acts in the CNS as an excitatory neurotransmitter.
引用
收藏
页码:249 / 256
页数:8
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