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Concentration-dependent substrate behavior of native AMPA receptors

NATURE NEUROSCIENCE 2000年第10期3卷 992-997页

作者： Smith, TC Howe, JR Yale Univ Sch Med Dept Pharmacol New Haven CT 06520 USA

AMPA-type glutamate receptors mediate most excitatory postsynaptic currents (EPSCs) at central synapses, and their conductance determines in part the size of EPSCs. The conductance of a recombinant AMPA receptor depends on the number of agonist molecules bound to the channel. Here we tested whether native AMPA and kainate receptors show this behavior in outside-out patches from neurons in situ by measuring conductance levels of single channels over a wide range of agonist concentrations. We found that the conductance of AMPA, but not kainate, receptors depended strongly on agonist concentration. Our results suggest that alterations in the glutamate concentration in the synaptic cleft may change the apparent unitary conductance of postsynaptic AMPA receptors.

关键词：动物新生剂量效应关系药物兴奋性氨基酸拮抗剂/药理学兴奋性突触后电位/药物作用兴奋性突触后电位/生理学谷氨酸/代谢谷氨酸/药理学离子通道/药物作用离子通道/代谢红藻氨酸/类似物和衍生物红藻氨酸/药理学小鼠近交C57BL 神经肌肉去极化药/药理学器官培养技术喹恶啉类/药理学受体 AMPA/激动剂受体 AMPA/药物作用受体 AMPA/代谢受体红藻氨酸/激动剂受体红藻氨酸/药物作用受体红藻氨酸/代谢突触膜/药物作用突触膜/代谢动物小鼠

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Mutation of a glutamate receptor motif reveals its role in gating and δ2 receptor channel properties

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NATURE NEUROSCIENCE 2000年第4期3卷 315-322页

作者： Kohda, K Wang, Y Yuzaki, M St Jude Childrens Res Hosp Dept Dev Neurobiol Memphis TN 38105 USA

Despite its importance in the cerebellum, the functions of the orphan glutamate receptor delta 2 are unknown. We examined a mutant delta 2 receptor channel in lurcher mice that was constitutively active in the absence of ligand. Because this mutation was within a highly conserved motif (YTANLAAF), we tested its effect on several glutamate receptors. Mutant delta 2 receptors showed distinct channel properties, including double rectification of the current-voltage relationship, sensitivity to a polyamine antagonist and moderate Ca2+ permeability, whereas other constitutively active mutant glutamate channels resembled wildtype channels in these respects. Moreover, the kinetics of ligand-activated currents were strikingly altered. We conclude that the delta 2 receptor has a functional ion channel pore similar to that of glutamate receptors. The motif may have a role in the channel gating of glutamate receptors.

关键词：氨基酸序列氨基酸取代抗焦虑药/药理学抗高血压药/药理学苯二氮|艹卓|类苯噻二嗪/药理学细胞系保守序列地卓西平马来酸盐/药理学兴奋性氨基酸激动剂/药理学兴奋性氨基酸拮抗剂/药理学谷氨酸/药理学离子通道闸门/药物作用离子通道闸门/遗传学红藻氨酸/类似物和衍生物红藻氨酸/药理学肾/细胞学小鼠神经学突变型分子序列数据诱变/生理学神经肌肉去极化药/药理学膜片钳术浦肯野细胞/化学浦肯野细胞/生理学喹恶啉类/药理学受体谷氨酸/化学受体谷氨酸/遗传学受体谷氨酸/代谢转染动物人类小鼠

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Quantal evoked depolarizations underlying the excitatory junction potential of the guinea-pig isolated vas deferens

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JOURNAL OF PHYSIOLOGY-LONDON 1999年第2期520卷 527-537页

作者： Manchanda, R Venkateswarlu, K Indian Inst Technol Sch Biomed Engn Bombay 400076 Maharashtra India

1. The effects of a putative gap junction uncoupling agent, heptanol, on the intracellularly recorded junction potentials of the guinea-pig isolated ras deferens have been investigated. 2. After the stimulation-evoked excitatory junction potentials (EJPs) had been suppressed by heptanol (2.0 mM) to undetectable levels, a different pattern of evoked activity ensued. This consisted of transient depolarizations: that were similar to EJPs in being stimulus locked and in occurring at a fixed latency, but differed from EJPs in that they occurred intermittently and had considerably briefer time courses. 3. Analysis of the amplitudes and temporal parameters of the rapid residual depolarizations revealed a close similarity with spontaneous EJPs (SEJPs). There was no statistically significant difference between the rise times, time constants of decay and durations of the rapid residual depolarizations and of SEJPs. 4. Selected evoked depolarizations were virtually identical to SEJPs occurring in the same cell. Evoked depolarizations of closely similar amplitude and time course also occurred, usually within a few stimuli of each other. 5. These depolarizations appear to represent the individual quantal depolarizations that normally underlie the EJP and are therefore termed 'quantal excitatory junction potentials' (QEJPs) to distinguish them from both EJPs and SEJPs. 6. We examined the possibility that heptanol revealed QEJPs by disrupting electrical coupling between cells in the smooth muscle syncytium. Heptanol (2.0 mM) had no effect on the amplitude distribution, time courses, or the frequency of occurrence of SEJPs. Intracellular input impedance (R-in) of smooth muscle cells was left unaltered by heptanol. 7. 'Cable' potentials of the vas deferens, recorded using the partition stimulation method, also remained unchanged in the presence of heptanol. Thus, heptanol appeared not to modify syncytial electrical properties of the smooth muscle in any significant way. 8. Our obser

关键词：电生理学缝隙接合部/药物作用庚醇/药理学肌平滑血管/药物作用神经肌肉去极化药/药理学神经肌肉接头/药物作用突触传递/药物作用输精管/药物作用动物豚鼠男(雄)性

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Pharmacological characterization of endogenous acetylcholine release from primary septal cultures

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第2期292卷 692-697页

作者： Auld, DS Day, JC Mennicken, FO Quirion, E Douglas Hosp Res Ctr Verdun PQ H4H 1R3 Canada McGill Univ Fac Med Dept Neurol & Neurosurg Montreal PQ Canada McGill Univ Fac Med Dept Pharmacol & Therapeut Montreal PQ Canada McGill Univ Fac Med Dept Psychiat Montreal PQ Canada

A detailed investigation of endogenous acetylcholine (ACh) release from primary embryonic septal cultures is described in this study. Applications of veratridine (25 mu M) or increasing extracellular concentrations of K+ (6-100 mM) induced robust increases of endogenous ACh release (similar to 500-15,000 fmol/well/10 min). Release stimulated with K+ (25 mM) was sustainable and did not differ significantly over 180 min. ACh release was dependent on extracellular choline and decreased proportionally to choline concentrations (0-10 mu M). For example, after 30 min of stimulation with K+ (25 mM), release in the absence of extracellular choline was similar to 25% of that associated with 10 mM choline. The vesicular transport blocker vesamicol (0-5 mu M) almost completely prevented stimulated and basal ACh release at the highest concentration evaluated, which suggests a mostly vesicular mode of release in this model. The M-2-like muscarinic receptor antagonist AF-DX 384 (0-10 mu M) enhanced stimulated ACh release (similar to 150% at the highest concentration evaluated), whereas the nonspecific muscarinic receptor agonist oxotremorine (0-10 mu M) decreased stimulated release (similar to 60% at the highest concentration evaluated), suggesting that functional muscarinic autoreceptors exist in primary embryonic septal cultures. Novel findings concerning ACh release from primary embryonic septal cultures are reported herein, and the demonstration of ACh release gives further credit to the use of these cultures for studying cholinergic system functioning and in relation to physiology and pathology.

关键词：乙酰胆碱/分泌细胞培养的胆碱/生理学胆碱O-乙酰转移酶/代谢色谱法高压液相剂量效应关系药物药物相互作用胚胎哺乳动物/代谢毒蕈碱激动剂/药理学神经肌肉去极化药/药理学氧代震颤素/药理学抗副交感神经药/药理学哌啶类/药理学哌仑西平/类似物和衍生物哌仑西平/药理学钾/药理学脑中隔/代谢时间因素藜芦定/药理学动物大鼠

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DEPOLARIZING EFFECTS OF IONOPHORES X-537A AND A23187 AND THEIR RELEVANCE TO SECRETION

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BRITISH JOURNAL OF PHARMACOLOGY 1975年第3期54卷 400-402页

作者： COCHRANE, DE DOUGLAS, WW YALE UNIV SCH MED DEPT PHARMACOL NEW HAVEN CT 06510 USA

The ionophore X-537A depolarized frog skeletal muscle fibres about 10 mV in 10 min and a further 30 mV or so over the next 50 minutes. With A23187, depolarization was relatively feeble and delayed in onset but was hastened when calcium was removed from the bathing medium. The results support conjecture that some functional responses to these ionophores are attributable, in part, to depolarization.

关键词：抗菌药/药理学卡西霉素/药理学拉沙洛西/药理学膜电位/药物作用肌/药物作用肌/生理学神经肌肉去极化药/药理学豹纹蛙时间因素动物

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Rapacuronium (Org9487): do we have a replacement for succinylcholine?

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BRITISH JOURNAL OF ANAESTHESIA 1999年第4期82卷 489-492页

作者： Goulden, MR Hunter, JM Univ Liverpool Clin Dept Dept Anaesthesia Liverpool L69 3GA Merseyside England

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小剂量非去极化肌松药用于面神经监测手术麻醉的临床观察

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中国医师杂志 2009年第5期11卷 704-706页

作者：朱茂恩郭曲练邹望远马新华中南大学湘雅医院麻醉科湖南长沙410008

目的观察小剂量非去极化肌松药在面神经监测手术麻醉中的临床应用。方法30例全麻下术中行面神经功能监测的听神经瘤切除术患者，ASAⅠ级或Ⅱ级，使用TOF-watch sx肌松监测仪监测肌松程度，随机分成2组（n=15）：使用小剂量肌松药维持组... 详细信息

目的观察小剂量非去极化肌松药在面神经监测手术麻醉中的临床应用。方法30例全麻下术中行面神经功能监测的听神经瘤切除术患者，ASAⅠ级或Ⅱ级，使用TOF-watch sx肌松监测仪监测肌松程度，随机分成2组（n=15）：使用小剂量肌松药维持组（R组）和对照组（C组），R组麻醉诱导后泵入非去极化肌松药维持TOF=3，C组诱导后至面神经监测结束不再使用肌松药，观察收缩压（SP），舒张压（DP），心率（HR），脉搏氧饱和度（SpO2），呼气末CO2分压（PETCO2）。观察有无术中体动反应，术后第1天回访患者，测定面神经功能H-B分级。结果所有病人均满意完成面神经监测，C组有3例患者术中发生体动，R组无术中体动发生，2组病人术后面神经功能优良率（H—B分级1～2级）差异无统计学意义。结论肌松监测下，小剂量非去极化肌松药可以用于面神经监测手术麻醉，并能减少术中体动的发生。

关键词：神经肌肉去极化药/药理学面神经神经瘤听/外科学麻醉

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