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21.
Ineffectiveness of organic calcium channel blockers in antagonizing long-term potentiation 总被引:1,自引:0,他引:1
Evidence has accumulated suggesting that the presence of calcium is critical for development of hippocampal long-term potentiation (LTP). However, there is a paucity of information about whether calcium's role in LTP is pre- or postsynaptic. In the present study, we examined the effectiveness of nitrendipine, verapamil, flunarizine and the benzodiazepine diazepam in: blocking voltage-dependent calcium channels; blocking synaptic transmission; and preventing development of LTP. Using the in vitro slice preparation, we obtained intracellular and extracellular recordings from guinea pig hippocampal CA1 pyramidal cells. At the cellular level, all 4 drugs were ineffective in blocking voltage-dependent calcium spikes (TTX resistant) and the calcium-dependent afterhyperpolarization. Verapamil and diazepam appeared to antagonize synaptic transmission, as reflected in smaller population spike amplitudes. Development of long-term potentiation was not affected by the presence of verapamil, flunarizine and diazepam. Nitrendipine appeared to reduce the percentage of slices exhibiting LTP; however, ethanol, the vehicle used to dissolve nitrendipine, was shown in separate experiments to reduce the percentage of slices exhibiting LTP. These results suggest that neither the organic calcium channel blockers--nitrendipine, verapamil, and flunarizine--nor micromolar concentrations of diazepam are potent blockers of extrasynaptic voltage-sensitive calcium channels in hippocampus. They thus cannot be used to demonstrate a specific pre- or postsynaptic calcium role in LTP. 相似文献
23.
Severe myoclonic epilepsy (SMEI) or Dravet syndrome is caused by mutations of the SCN1A gene that encodes voltage-gated sodium channel alpha-1 subunit. Recently, we generated and characterized a knock-in (KI) mice with an SCN1A nonsense mutation that appeared in three independent SMEI patients. The SCN1A-KI mice well reproduced the SMEI disease phenotypes. Both homozygous and heterozygous knock-in mice developed epileptic seizures within the first postnatal month. In heterozygous knock-in mice, trains of evoked action potentials in inhibitory neurons exhibited pronounced spike amplitude decrement late in the burst but not in pyramidal neurons. We further showed that in wild-type mice the Nav1.1 protein is expressed dominantly in axons and moderately in somata of parbalbumin (PV) – positive inhibitory interneurons. Our immunohistochemical observations of the Nav1.1 are clearly distinct to the previous studies, and our findings has corrected the view of the Nav1.1 protein distribution. The data indicate that Nav1.1 plays critical roles in the spike output from PV interneurons and further, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures in the mice. These information should contribute to the understanding of molecular pathomechanism of SMEI and to develop its effective therapies. 相似文献
24.
Birgit T Priest Kenneth M Blumenthal Jaime J Smith Vivien A Warren McHardy M Smith 《Toxicon》2007,49(2):194-201
The tarantula venom peptides ProTx-I and ProTx-II inhibit voltage-gated sodium channels by shifting their voltage dependence of activation to a more positive potential, thus acting by a mechanism similar to that of potassium channel gating modifiers such as hanatoxin and VSTX1. ProTx-I and ProTx-II inhibit all sodium channel (Nav1) subtypes tested with similar potency and represent the first potent peptidyl inhibitors of TTX-resistant sodium channels. Like gating modifiers of potassium channels, ProTx-I and ProTx-II conform to the inhibitory cystine knot motif, and ProTx-II was demonstrated to bind to sodium channels in the closed state. Both toxins have been synthesized chemically, and ProTx-II, produced by recombinant means, has been used to map the interaction surface of the peptide with the Nav1.5 channel. In comparison, beta-scorpion toxins activate sodium channels by shifting the voltage dependence of activation to more negative potentials, and together these peptides represent valuable tools for exploring the gating mechanism of sodium channels. 相似文献
25.
异丙酚对豚鼠耳蜗外毛细胞钙离子移动的影响 总被引:1,自引:1,他引:0
目的观察不同浓度异丙酚对氯化钾诱发的豚鼠耳蜗外毛细胞内钙离子移动的影响,探讨其对听觉外周感受器(耳蜗)作用的可能机制。方法用Fluo-3AM荧光指示剂染色急性分离的豚鼠耳蜗外毛细胞,在激光共聚焦显微镜下动态观察使用异丙酚前及异丙酚(50、250μmol/L)预处理后,氯化钾诱发的细胞内钙离子浓度的变化。结果异丙酚可使氯化钾诱发的外毛细胞内钙荧光染色强度的峰值下降,较对照组有明显差异,并与浓度呈正相关。结论异丙酚浓度依赖性地降低耳蜗外毛细胞内钙离子浓度,部分与抑止细胞外钙内流有关。 相似文献
26.
成都郊区学龄前儿童钙营养及骨矿状况的调查 总被引:2,自引:1,他引:1
目的:了解郊区学龄前儿童的膳食钙营养及骨矿发育状况。方法:随机选取成都郊区两所幼儿园,对161名3~6岁儿童进行膳食调查,检测血钙、尿钙,并用DEXA法、超声骨量分别测腰椎骨矿及跟骨骨量。结果:郊区学龄前儿童膳食钙营养状况仍较差。只达推荐量的32%左右;低血钙、低尿钙百分率分别为42.24%、63.34%;骨量、骨密度、骨面积与体重、身高呈正相关,学龄前儿童已表现出骨密度差异,男孩较女孩高,郊区学龄前儿童骨矿状况较城市同龄儿童为低。结论:郊区学龄前儿童由于膳食结构不合理。钙营养不足,低尿钙、血钙发生率较高,骨量发育较城市明显落后。必须加强人们对钙营养重要性的认识,调整膳食结构,多食人奶制品、豆制品等含钙丰富的食物,改普钙营养状况。促进达到最佳骨量。 相似文献
27.
Treatment of frog neuromuscular preparations with chlorpromazine (5 mumol/l) resulted in a marked rise in miniature endplate potential (MEPP) frequency of greater than 100% within 30 min, and an increase in evoked transmitter release (quantal content 5-15) of about 35%. Treatment with chlorpromazine sulphoxide (5 microM), a derivative of chlorpromazine with a much lower affinity for calmodulin, had very little effect on either form of transmitter release. It is concluded that stimulatory effects of calmodulin-binding drugs at the nerve terminal may well be exerted through calmodulin inhibition. The stimulatory effect of chlorpromazine on MEPP frequency was markedly reduced in preparations bathed in EGTA-containing Ca2+-free saline, but the response was largely restored by raising the temperature by 3-4 degrees C. It is argued that despite this partial dependence on [Ca2+]o, stimulation of transmitter secretion by chlorpromazine is likely to be mediated by inhibition of calmodulin-activated Ca2+-ATPases, and consequent elevation of [Ca2+]i. 相似文献
28.
氢氧化钙预防根管治疗期间急症的临床观察 总被引:1,自引:1,他引:0
目的 观察氢氧化钙根管内封药对预防根管治疗期间急症的临床疗效。方法 使用氢氧化钙及传统根管内消毒药物樟脑对氯酚、甲醛甲酚根管内封药,观察疼痛指数并比较其根管治疗期间急症的发生率。结果 氢氧化钙封药后根管治疗期间急症的发生率最低,与传统药物相比,其差异有统计学意义。结论 氢氧化钙根管内封药。对预防根管治疗期间的急症有较好的作用。 相似文献
29.
CFTR was reported to regulate ENaC channel opening, decreasing ENaC activity in airways and increasing it in sweat ducts. We generated MDCK-I cell lines stably expressing tagged alphabetagammaENaC+CFTR or ENaC alone, and developed an assay to quantify cell-surface half-life of ENaC. Surprisingly, we found that co-expressed CFTR stabilizes ENaC at the plasma membrane, suggesting that CFTR regulates ENaC stability, not just opening. 相似文献
30.
磷酸钙水泥填充固定桡骨远端骨折的抗旋转生物力学研究 总被引:1,自引:1,他引:0
目的对磷酸钙水泥(CPC)填充固定桡骨远端骨折的抗旋转应力进行评价,并与传统的克氏针固定方法进行比较。方法18根人桡骨标本制备桡骨远端骨折伴骨缺损模型,随机分为三组:克氏针固定组、CPC固定组和CPC 克氏针联合固定组。设定扭转速度为5°/min,最大扭转角度为10°时停止。记录扭转刚度、10°内的最大扭矩及所对应的最大扭角。结果在10°的扭转范围内,CPC固定组、CPC 克氏针联合固定组的扭转刚度、最大扭矩均比克氏针固定组大,差异有统计学意义(P< 0.01);最大扭转角度分别为4.3°和5.0°,均比克氏针组(9.6°)小,差异有统计学意义(P<0.01)。CPC固定组与CPC 克氏针联合固定组之间的扭转刚度、最大扭矩及最大扭角差异无统计学意义(P> 0.05)。结论在旋转角度小于4°范围内,CPC的抗旋转固定强度要比克氏针大,超过这个范围,骨水泥就会发生断裂,CPC的有效固定范围比克氏针要小。 相似文献