共查询到19条相似文献,搜索用时 156 毫秒
1.
目的:探讨内源性硫化氢(H2S)对血管紧张素II(Ang II)引起的延髓神经元活性氧(ROS)水平升高的作用及其可能机制。方法:首先培养原代延髓神经元;免疫荧光双标法鉴定神经元及内源性H2S生成酶胱硫醚β-合成酶(CBS)在神经元的表达;同时或单独给予Ang II (1 μmol/L)和丁酸钠(NaBu,一种CBS激动剂;100 μmol/L、250 μmol/L和500 μmol/L),二氢乙啶荧光探针法测定ROS水平;采用总超氧化物歧化酶(SOD)活性检测试剂盒观察总SOD的活性;real-time PCR观察CBS mRNA的表达。结果:(1)原代培养的90% 以上的细胞为神经元,Ang II(1 μmol/L)升高延髓神经元ROS水平;(2)Ang II抑制神经元总SOD的活性;(3)荧光双标显示CBS在延髓神经元有表达,Ang II可降低CBS mRNA的表达;(4)NaBu(250 μmol/L和500 μmol/L)显著抑制Ang II引起的ROS水平的升高,且呈剂量依赖性效应。而NaBu单独对延髓神经元ROS水平作用不明显。结论:Ang II引起的延髓神经元ROS水平升高至少部分是通过降低总SOD的活性和CBS mRNA的表达而实现的;而内源性H2S可能通过相反的作用抑制这一过程。 相似文献
2.
目的: 探讨硫化氢(H2S)对血管紧张素II(angiotensin II,Ang II)所致延髓神经元活性氧(reactive oxygen species,ROS)水平变化的影响,以及H2S抗氧化应激的相关机制。方法: 采用原代培养的延髓神经元,分组如下:对照组、Ang II处理组、硫氢化钠(NaHS)处理组、NaHS+Ang II处理组和PD98059(p-ERK1/2蛋白的抑制剂)+ Ang II处理组。选用二氢乙啶(DHE)荧光探针法测定各组神经元胞内的ROS水平,Western blotting检测ERK1/2和p-ERK1/2蛋白的表达量,CCK-8法测定神经元的活性。结果: Ang II(终浓度为100 nmol/L)引起神经元ROS水平升高;NaHS(50~200 μmol/L)明显抑制Ang II引起的神经元ROS水平升高,但单独给予NaHS并不影响神经元ROS水平;p-ERK1/2蛋白的抑制剂PD98059也能明显抑制Ang II引起的神经元ROS水平的升高;适宜作用浓度的NaHS能够显著降低Ang II引起的神经元p-ERK1/2蛋白表达。结论: H2S能够显著抑制Ang II引起的神经元ROS水平升高,其作用机制与MAPK家族中p-ERK1/2蛋白的表达有关。H2S可能通过降低p-ERK1/2的表达量而产生抗氧化应激作用。 相似文献
3.
目的:探讨降钙素基因相关肽(CGRP)对大鼠胃平滑肌的调控作用。方法:贴块法原代培养大鼠胃平滑肌细胞,特异性平滑肌肌动蛋白α-actin免疫细胞化学鉴定。实验分CGRPⅠ组(10~(-7)mol/LCGRP)、CGRPⅡ组(10~(-8)mol/L CGRP)、CGRPⅢ组(10~(-9)mol/L CGRP)和干预组(10~(-6)mol/LCGRP 8-37)与空白对照组。图像分析系统测定大鼠胃平滑肌细胞长度;Ca~(2+)荧光指示剂测定细胞内Ca~(2+)浓度;CellTiter-Glo~试剂盒检测细胞内ATP含量。结果:CGRP可舒张胃平滑肌细胞,降低胃平滑肌细胞游离Ca~(2+)浓度及ATP含量。结论:CGRP通过受体介导直接参与胃平滑肌细胞松弛;CGRP可能通过降低胃平滑肌细胞游离Ca~(2+)浓度、ATP含量而发挥其调控作用。 相似文献
4.
本工作探讨VIP在下丘脑水平对PRL和β-EP释放的调节,结果表明,所用三种剂量的VIP均显著兴奋PRL的释放,兴奋效应与VIP剂量相关;各剂量VIP对β-EP的释放均无明显影响,提示VIP可经某种下丘脑机制兴奋PRL的释放。我们的结果还进一步证明,VIP兴奋PRL的释放似与抑制DA的作用无关。另外,应用体外培养的正常大鼠前叶垂体细胞,观察10~(-10)~10~(-6)mol/L的VIP对PRL和β-EP释放的影响及其与细胞外Ca~(2+)浓度的关系,看到VIP可直接兴奋垂体细胞释放PRL,且具剂量相关效应;VIP兴奋PRL的释放与胞外Ca~(2+)浓度无关。剂量达10~(-7)mol/L的VIP仍不影响垂体细胞β-EP的释放。另用新鲜制备的正常大鼠离散前叶垂体细胞,比较VIP对细胞内cAMP和胞内Ca~(2+)的影响,结果表明,10~(-7)mol/L的VIP显著升高细胞内Ca~(2+)浓度,也显著升高胞内cAMP的水平,但后者可被2.0mmol/L EGTA消除,说明胞内cAMP水平的改变有赖于胞外Ca~(2+)的存在,联想上述VIP兴奋PRL的释放却与胞外Ca~(2+)的存在与否无关,提示VIP兴奋PRL的释放似由胞内Ca~(2+)而非cAMP介导信息跨膜传递。 相似文献
5.
魏晟 《医学分子生物学杂志》1993,(5)
本文运用fura-2技术研究了K~+通道阻滞剂对Carbacol(氨甲酰胆碱)介导的Ca~(2+)进入人类排Cl~-的HT-29/B6并影响胞内钙浓度的作用。结果表明,用100μmol/L氨甲酰胆碱刺激HT-29/B6可产生清晰的双相Ca~(2+)反应:Ca从静息水平(85±3nmol/L)迅速激发至短暂的峰值(821±44nmol/L),随后降至一段平台(317±12nmol/L)。平台高度与胞外Ca~(2+)浓度相关并在Ca~(2+)出入胞浆膜之间代表着新的平衡状态。平台在缺Ca~(2+)的条件下不出现而钙峰无论在有钙或无钙条件下均能出现,这表明Ca~(2+)峰的出现是由胞内Ca~(2+)库释放所致,而平台的维持则是外钙流入胞内所致。加阿托品 相似文献
6.
《中国病理生理杂志》2019,(11)
目的:探讨黄芪甲苷(ASⅣ)对血管紧张素Ⅱ(Ang Ⅱ)诱导的心肌H9c2细胞凋亡的作用及其机制。方法:用不同浓度Ang Ⅱ及ASⅣ处理心肌H9c2细胞,CCK-8法检测Ang Ⅱ及ASⅣ对心肌细胞活力的影响,选取Ang Ⅱ的最佳作用浓度为1μmol/L,ASⅣ浓度梯度设为25、50和100μmol/L。实验分为6组:对照组、ASⅣ组、Ang Ⅱ组、Ang Ⅱ+ASⅣ (25μmol/L)组、Ang Ⅱ+ASⅣ (50μmol/L)组和Ang Ⅱ+ASⅣ (100μmol/L)组。倒置相差显微镜下观察细胞形态并进行细胞计数检测细胞生长情况,TUNEL法检测细胞凋亡,DCFH-DA标记法检测活性氧簇(ROS)的水平, Western blot法检测Bax、Bcl-2、核因子E2相关因子2(Nrf2)及其下游因子血红素加氧酶1(HO-1)的表达情况。用negative control shRNA(NC)或Nrf2-shRNA(shRNA)质粒转染H9c2细胞,转染后实验分为8组,NC+control组、NC+AngⅡ组、NC+ASⅣ组、NC+AngⅡ+ASⅣ组、shRNA+control组、shRNA+AngⅡ组、shRNA+ASⅣ组和shRNA+AngⅡ+ASⅣ组,检测各组ROS水平及Nrf2和HO-1蛋白表达情况。结果:Ang Ⅱ呈浓度依赖性降低心肌H9c2细胞的活力,ASⅣ能逆转Ang Ⅱ对心肌H9c2细胞活力降低的作用,并呈浓度依赖性(P0.05);与对照组相比,Ang Ⅱ组细胞凋亡率显著增加,ROS水平显著升高,Bax蛋白表达水平显著升高,Bcl-2、Nrf2和HO-1蛋白表达水平显著降低;与Ang Ⅱ组相比,ASⅣ可呈浓度依赖性逆转Ang Ⅱ诱导的心肌细胞凋亡率升高情况,降低ROS水平,下调Bax蛋白表达水平,上调Bcl-2、Nrf2和HO-1蛋白的表达水平(P0.05)。转染shRNA后,ASⅣ降低Ang Ⅱ诱导的ROS产生及上调Nrf2和HO-1表达的作用被消除。结论:ASⅣ抑制Ang Ⅱ诱导的心肌H9c2细胞凋亡,这一保护作用与其降低ROS水平、介导Nrf2/HO-1信号通路相关。 相似文献
7.
目的:观察番茄红素(lycopene)对氧化损伤的原代皮质神经元的保护效应并探讨其作用机制。方法:采用原代细胞培养技术体外分离培养小鼠皮质神经元,通过免疫荧光染色法检测微管相关蛋白2(microtubuleassociated protein 2,MAP-2)的表达进行鉴定。将神经元分为4组:正常神经元组、叔丁基过氧化氢(tert-butyl hydroperoxide,t-BHP)处理组、t-BHP+lycopene处理组和lycopene处理组,培养24 h,采用MTT法检测各组神经元的活力;采用流式细胞技术检测各组神经元内ROS的水平;Western blot法检测各组神经元Bax、Bcl-2、caspase-3、cleaved caspase-3及细胞色素C蛋白表达的变化。结果:Lycopene能明显提高t-BHP处理的神经元活性,降低tBHP处理的神经元内ROS含量,同时上调Bcl-2蛋白的表达,降低Bax、cleaved caspase-3和细胞色素C蛋白的表达(P0.05)。结论:Lycopene能够对抗t-BHP诱导的原代皮质神经元的损伤,抑制神经元凋亡,其机制可能与降低神经元内ROS的水平及上调的表达有关。 相似文献
8.
目的:建立NMDA诱导原代培养皮层神经元兴奋毒损伤模型,探讨NMDA对NMDA受体过度活化诱导兴奋性神经毒的可能途径。方法:原代培养新生大鼠大脑皮层神经元,通过倒置显微镜形态学观察、细胞活力检测(MTT及LDH释放的检测)及胞内Ca2+的动态测定,探索NMDA诱导毒性作用的适当浓度及时间。通过对ROS、NO检测,分析NMDA诱导毒性作用于线粒体的损伤情况。结果:NMDA(100μmol/L/2 h)引起皮层神经元形态学改变,且引起神经元细胞活力时间和浓度依赖性的下降,由同时伴随LDH释放增加(P<0.05),ROS和NO的生成量明显增加(P<0.05),皮层神经元内Ca2+的快速升高,并维持在高水平。结论:NMDA诱发皮层神经元明显的细胞毒性作用,提示NMDA过度活化NMDA受体后通过神经元膜内Ca2+超载造成ROS和NO的生成量增加,导致皮层神经元产生毒性损伤。 相似文献
9.
IP_3R、RYR与Ca~(2+)信号 总被引:1,自引:0,他引:1
陈政良 《医学分子生物学杂志》1994,(5)
Ca~(2+)在生命活动中起着至关重要的作用。细胞接受外界刺激后,通过胞膜转导,将信息传入胞内。胞内两大Ca~(2+)通道家族——三磷酸肌醇受体(IP_3R)和斯里兰卡向桂碱(ryanodine,RY)受体(RYR)将胞内信息以周期性的Ca~(2+)波动或振动编码,并藉此形式将所载信息传递给相应的受体,从而诱导复杂的生物学应答。本文在介绍IP_3R和 RYR cDNA克隆、受体结构与功能的关系及其活性调节的基础上,讨论IP_3R和RYR介导胞内Ca~(2+)信号产生及传递的分子机制。 相似文献
10.
目的:观察血红素加氧酶(HO)在AngⅡ致血管平滑肌细胞(VSMCs)增殖和肥大中的作用并探讨其可能机制。方法:(1)免疫印迹法测定平滑肌细胞HO-1蛋白表达水平;(2)β-液体闪烁记数仪测定[3H]-TdR和[3H]-亮氨酸掺入量;(3)乙酰乙酸双氯荧光素(DCFH-DA)法测定平滑肌细胞内活性氧(ROS)水平。结果:(1) Hemin组HO-1蛋白表达水平与对照组和AngⅡ组相比均明显升高(P<0.01)。(2)AngⅡ使血管平滑肌细胞[3H]-TdR和[3H]-亮氨酸掺入量较对照组分别升高20.7%和18.0%(P<0.01),而给予HO底物Hemin则抑制了[3H]-TdR和[3H]-亮氨酸掺入量的增加, 给予HO的抑制剂ZnPPIX则可以促进AngⅡ所致的[3H]-TdR、[3H]-亮氨酸掺入量的增加。(3) AngⅡ组ROS水平明显高于对照组(P<0.01);Hemin组ROS水平较AngⅡ组降低了62.7%,而ZnPPIX组高于AngⅡ组39.5%。结论:HO可抑制AngⅡ所导致的VSMCs的增殖和肥大,其机制可能与减少细胞内ROS生成有关。 相似文献
11.
目的:观察红细胞生成素(erythropoietin,EPO)对过氧化氢(H_2O_2)刺激后红细胞衰亡(eryptosis)和红细胞中活性氧簇(reactive oxygen species,ROS)生成的影响,并探讨其可能机制。方法:将1%健康人红细胞悬液在以下3组不同的体外培养液中孵育:对照组(C组,培养基为PBS液)、H_2O_2组(H组,培养基为H_2O_2终浓度100μmol/L的PBS液)和EPO组(E组,培养基为H_2O_2终浓度100μmol/L、EPO终浓度2×10~4U/L的PBS液)。分别在孵育24 h和60 h时,留取红细胞以备检测。使用流式细胞术检测红细胞的衰亡率、红细胞内ROS和红细胞内钙离子浓度(_i~([Ca2+])),观察各检测指标的变化并分析其相关性。结果:红细胞衰亡率在C组随孵育时间延长而增加,在相同观察时点,H组较C组明显增加(P0.01),E组较H组明显降低(P0.01)。H组红细胞的ROS生成较C组明显增多,_i~([Ca2+])较C组明显升高(P0.01);E组红细胞的ROS生成较H组明显减少,_i~([Ca2+])较H组明显降低(P0.05或P0.01)。结论:H_2O_2诱导健康红细胞加速衰亡,而EPO可以抑制H_2O_2诱导的红细胞衰亡,其机制可能与抗氧化及_i~([Ca2+])的改变有关。 相似文献
12.
In an attempt to probe the relationship between excitotoxicity and increases in intracellular calcium ([Ca2+]i), BAPTA-AM and its analogs were applied to cultured hippocampal neurons. Chelation of [Ca2+]i depressed and prolonged transient responses to glutamate and did not effect elevation of [Ca2+]i by prolonged exposure. This explains the inability of the chelators to prevent glutamate-induced toxicity. 相似文献
13.
目的:观察硫化氢的供体硫氢化钠(Na HS)对三磷酸腺苷(ATP)诱导的PC12细胞活力、胞内Ca2+浓度([Ca2+]i)及膜通透性的变化,探讨硫化氢神经保护作用的嘌呤信号机制。方法:将对数生长期高分化的PC12细胞,随机分为4组,分别为(1)正常对照组:常规培养,不进行ATP处理;(2)ATP组:接种细胞24 h后ATP处理;(3)Na HS+ATP组:Na HS预先孵育30 min后再用ATP处理,并且Na HS始终存在于反应体系中;(4)KN-62(P2X7受体阻断剂)+ATP组:KN-62预先孵育30 min,其余同Na HS+ATP组。MTT检测各组细胞活力,Fura-2/AM荧光染料检测各组[Ca2+]i,检测荧光染料YO-PRO-1的相对荧光单位以反映膜的通透性。结果:(1)0.3mmol/L ATP对细胞活力无影响,但1、3、5、10 mmol/L ATP则呈浓度依赖式明显降低细胞活力,200μmol/L Na HS干预可明显逆转ATP引起的细胞活力下降(P0.05),而800μmol/L Na HS预处理则加剧ATP对PC12细胞的损伤(P0.05)。(2)ATP处理PC12细胞会引起[Ca2+]i迅速升高并且呈浓度依赖性,Na HS预处理能对抗ATP引起的[Ca2+]i升高(P0.05)。(3)随着ATP浓度的增加及作用时间的延长,PC12细胞内YO-PRO-1的荧光强度显著增加,Na HS预处理可明显减少细胞对YO-PRO-1的摄取(P0.05)。结论:硫化氢可保护ATP损伤的PC12细胞,可能与其抑制[Ca2+]i升高和YO-PRO-1荧光增强有关。 相似文献
14.
Cytosolic free calcium ([Ca2+]i) was measured using fluorescent digital imaging microscopy in rat dorsal root ganglion neurons isolated from animals of two age groups (adult: seven months; and old: 30 months). Neurons were enzymatically isolated and maintained in primary culture for 14 days. Cultured neurons were loaded with the fluorescent dye, Fura-2. The spatial distribution of resting [Ca2+]i was even in both adult and old rats, but the value of cytoplasmic free calcium in old neurons was significantly higher (207 ± 37 nmol/l vs96 ± 23 nmol/l) in comparison with adult ones. Depolarization with 50 mmol/l K+ produced a rapid increase in [Ca2+]i in all neurons, but the values of depolarization-induced increase of [Ca2+]i in old neurons were significantly lower (423 ± 54 nmol/l) compared with cells isolated from adult rats (1011 ± 91 nmol/l). The time of the complete restoration of [Ca2+]i to the resting level was 10-times longer in old neurons. The caffeine-induced rise of intracellular calcium was somewhat higher in neurons from old animals, and its restoration to normal level was delayed.
The findings indicate a substantial alteration of the mechanisms of regulation of intracellular calcium homeostasis with neuronal ageing. 相似文献
15.
Astrocytes in the rat thalamus display spontaneous [Ca2+]i oscillations that are due to intracellular release, but are not dependent on neuronal activity. In this study we have investigated the mechanisms involved in these spontaneous [Ca2+]i oscillations using slices loaded with Fluo-4 AM (5 μM) and confocal microscopy. Bafilomycin A1 incubation had no effect on the number of spontaneous [Ca2+]i oscillations indicating that they were not dependent on vesicular neurotransmitter release. Oscillations were also unaffected by ryanodine. Phospholipase C (PLC) inhibition decreased the number of astrocytes responding to metabotropic glutamate receptor (mGluR) activation but did not reduce the number of spontaneously active astrocytes, indicating that [Ca2+]i increases are not due to membrane-coupled PLC activation. Spontaneous [Ca2+]i increases were abolished by an IP3 receptor antagonist, whilst the protein kinase C (PKC) inhibitor chelerythrine chloride prolonged their duration, indicating a role for PKC and inositol 1,4,5,-triphosphate receptor activation. BayK8644 increased the number of astrocytes exhibiting [Ca2+]i oscillations, and prolonged the responses to mGluR activation, indicating a possible effect on store-operated Ca2+ entry. Increasing [Ca2+]o increased the number of spontaneously active astrocytes and the number of transients exhibited by each astrocyte. Inhibition of the endoplasmic reticulum Ca2+ ATPase by cyclopiazonic acid also induced [Ca2+]i transients in astrocytes indicating a role for cytoplasmic Ca2+ in the induction of spontaneous oscillations. Incubation with 20 μM Fluo-4 reduced the number of astrocytes exhibiting spontaneous increases.
This study indicates that Ca2+ has a role in triggering Ca2+ release from an inositol 1,4,5,-triphosphate sensitive store in astrocytes during the generation of spontaneous [Ca2+]i oscillations. 相似文献
16.
Peter A. Anton Fergus Shanahan Xiao Ping Sun David Diehl Anatoly Kodner Emeran A. Mayer 《Immunopharmacology and immunotoxicology》1993,15(4):429-446
Vasoactive intestinal polypeptide (VIP) has been shown to stimulate adenylate cyclase in a human lymphoblast cell line (MOLT 4). In the present study, we monitored fluorescence in cell suspensions and in single fura-2 loaded MOLT 4 lymphoblasts to determine if VIP modulates intracellular calcium concentrations ([Ca2+]i), and if this modulation is mediated by adenylate cyclase. The distribution of [Ca2+]i in resting and stimulated cells was non-homogeneous, with gradients of high [Ca2+]i present in the subplasmalemmal space. In a subset of cells (10-30% of all cells studied), [Ca2+]i showed La3+-sensitive, temporal changes in the form of [Ca2+]i oscillations with a baseline [Ca2+]i value of 115±10 nM, an oscillation amplitude of 150±18 nM and a mean period of 9.2±2s. The remaining non-oscillating cells showed a constant [Ca2+]i level of 75±5 nM (n=65 cells from 4 experiments). In the subset of cells with spontaneous [Ca2+]i oscillations, VIP dose-dependendy (10-12 to 10-8M) increased the amplitude of oscillations but did not stimulate their frequency. The stimulatory effect of VIP was correlated with baseline [Ca2+]i in these cells, was attenuated in the presence of La3+ (25 μM), but was unaffected by cell depolarization (126 mM KC1). Dibutyryl cyclic AMP (10-4 to 10-3 M) and forskolin (10-4M) had no effect on [Ca2+]i oscillations, or on [Ca2+]i in cells without oscillations. In cell suspensions, baseline [Ca2+]i was found to be 55. 1±11.2 nM (meanS.E.M., n=11); VIP, cyclic AMP analogues or forskolin had no significant effect on [Ca2+]i. These findings suggest that: a) VIP modulates the amplitude of [Ca2+]i oscillations generated by a cytosolic [Ca2+] oscillator in a subset of cells at a concentration of 10-12M, a thousand-fold below the KD for the VIP receptor; b) baseline [Ca2+] values may be related to both the ability of cells to generate spontaneous [Ca2+] oscillations and of oscillating cells to respond to VIP; c) due to the small number of responding cells, VIP-induced [Ca2+]i changes are not detectable when studied in cell suspensions. 相似文献
17.
目的:探讨钙敏感受体(calcium-sensing receptor,Ca SR)在肺血管张力调节中的作用及信号途径。方法:采用Ⅱ型胶原酶消化法提取大鼠肺动脉平滑肌细胞(pulmonary artery smooth muscle cells,PASMCs),激光共聚焦扫描显微镜技术观察不同条件下PASMCs中钙离子浓度的变化,组织浴槽血管环技术观察血管张力的变化。结果:Ca SR激动剂(钙、钆)引起剂量依赖性的细胞内钙增加和血管张力增大,U73122和D609(PLC抑制剂)以及2-APB和肝素(IP3受体抑制剂)可减弱Ca SR的作用(P0.05),而U73343(U73122的无生物活性类似物)则无此作用(P0.05)。结论:Ca SR活化导致细胞内钙增加,进而引起肺动脉环收缩,这些过程是通过G蛋白-PLC-IP3信号转导通路实现的。 相似文献
18.
Roger P. Farrar S.Mehdi Rezazadeh Jim L. Morris Jo Ellen Dildy Kim Gnau Steven W. Leslie 《Neuroscience letters》1989,100(1-3):319-325
Several lines of experimental evidence support an association between altered Ca2+ regulation and aging. It has been supposed that free cytosolic Ca2+ concentrations ([Ca2+]i) may decrease or increase in aged animals. In this study, both resting and KCl-stimulated [Ca2+]i were measured in purified cortical synaptosomes from young (3 mo.), middle-aged (12 mo.), and old (24 mo.) Fischer 344 rats. Two additional groups of rats were included, one middle-aged and one old which were trained on a treadmill for 6 months prior to experimentation. The [Ca2+]i was determined using the fluorescent Ca2+ chelator fura-2. Net KCl-dependent changes (ΔK) in [Ca2+]i were determined by the difference between stimulatory (100 μM Ca2+/60 mM KCl) and resting (100 μM Ca2+/5 mM KCl buffer) conditions among the 3 age groups. Significant increases in [Ca2+]i were observed in each age group upon depolarization with 60 mM KCl. However, there were no significant age-dependent differences in either resting [Ca2+]i or KCl-stimulated [Ca2+]i. 相似文献
19.
The pro-inflammatory cytokine interleukin-1β (IL-1β) is released by cells during injury and stress, and increased neuronal expression of IL-1β is a feature of age-related neurodegeneration. We have recently reported that IL-1β has a biphasic effect on the K+-induced rise in intracellular Ca2+ concentration ([Ca2+]i) in cortical synaptosomes, exerting an inhibitory effect on the K+-induced rise in [Ca2+]i at lower (3.5 ng/mL) concentrations and a stimulatory effect on the K+-induced rise in [Ca2+]i at higher (100 ng/mL) concentrations. In the present study, we observed that the K+-induced rise in [Ca2+]i was inhibited to a similar extent by the lower concentration of IL-1β in cortical synaptosomes prepared from young (3-month-old), middle-aged (12-month-old) and aged (24-month-old) rats. In contrast, cortical synaptosomes prepared from the aged rats exhibited an increased susceptibility to the higher concentration of IL-1β, resulting in a marked elevation in [Ca2+]i. We propose that the age-related increase in neuronal concentration of IL-1β promotes a dramatic elevation in [Ca2+]i following membrane depolarization, thereby altering Ca2+ homeostasis and exacerbating neuronal vulnerability to excitotoxicity. 相似文献