Mechanisms of H+ modulation of glycinergic response in rat sacral dorsal commissural neurons

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	Mechanisms of H+ modulation of glycinergic response in rat sacral dorsal commissural neurons
	Li, YF ; Wu, LJ ; Li, Y ; Xu, L ; Xu, TL(徐天乐)
刊名	JOURNAL OF PHYSIOLOGY-LONDON
	2003
卷号	552 期号:1 页码:73-87
关键词	PROTON INHIBITION CALCIUM-CHANNEL NERVOUS-SYSTEM SPINAL-CORD AMILORIDE INHIBITION SELECTIVELY BLOCKS GANGLION NEURONS SPASMODIC MOUSE TISSUE ACIDOSIS HORN NEURONS
ISSN号	0022-3751
通讯作者	Xu, TL (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China,
英文摘要	Many ionotropic receptors are modulated by extracellular H+. So far, few studies have directly addressed the role of such modulation at synapses. In the present study, we investigated the effects of changes in extracellular pH on glycinergic miniature inhibitory postsynaptic currents (mIPSCs) as well as glycine-evoked currents (I-Gly) in mechanically dissociated spinal neurons with native synaptic boutons preserved. H+ modulated both the mIPSCs and I-Gly, biphasically, although it activated an amiloride-sensitive inward current by itself. Decreasing extracellular pH reversibly inhibited the amplitude of the mIPSCs and I-Gly, while increasing external pH reversibly potentiated these parameters. Blockade of acid-sensing ion channels (ASICs) with amiloride, the selective antagonist of ASICs, or decreasing intracellular pH did not alter the modulatory effect of H+ on either mIPSCs or I-Gly, H+ shifted the EC50 of the glycine concentration-response curve from 49.3 +/- 5.7 muM at external pH 7.4 to 131.5 +/- 8.1 muM at pH 5.5, without altering the Cl- selectivity of the glycine receptor (GlyR), the Hill coefficient and the maximal I-Gly, suggesting a competitive inhibition of I-Gly by H+. Both Zn2+ and H+ inhibited I-Gly. However, H+ induced no further inhibition of I-Gly in the presence of a saturating concentration of Zn2+. In addition, H+ significantly affected the kinetics of glycinergic mIPSCs and I-Gly. It is proposed that H+ and/or Zn2+ compete with glycine binding and inhibit the amplitude of glycinergic mIPSCs and I-Gly. Moreover, binding of H+ induces a global conformational change in GlyR, which closes the GlyR Cl- channel and results in the acceleration of the seeming desensitization of IGly as well as speeding up the decay time constant of glycinergic mIPSCs. However, the deprotonation rate is faster than the unbinding rate of glycine from the GlyR, leading to reactivation of the undesensitized GlyR after washout of agonist and the appearance of a rebound I-Gly. H+ also modulated the glycine cotransmitter, GABA-activated current (I-GABA). Taken together, the results support a 'conformational coupling' model for H+ modulation of the GlyR and suggest that W may act as a novel modulator for inhibitory neurotransmission in the mammalian spinal cord.
学科主题	Neurosciences & Neurology ; Physiology
收录类别	SCI
语种	英语
公开日期	2012-07-23
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/2002]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Li, YF,Wu, LJ,Li, Y,et al. Mechanisms of H+ modulation of glycinergic response in rat sacral dorsal commissural neurons[J]. JOURNAL OF PHYSIOLOGY-LONDON,2003,552(1):73-87.
APA	Li, YF,Wu, LJ,Li, Y,Xu, L,&Xu, TL.(2003).Mechanisms of H+ modulation of glycinergic response in rat sacral dorsal commissural neurons.JOURNAL OF PHYSIOLOGY-LONDON,552(1),73-87.
MLA	Li, YF,et al."Mechanisms of H+ modulation of glycinergic response in rat sacral dorsal commissural neurons".JOURNAL OF PHYSIOLOGY-LONDON 552.1(2003):73-87.