Regulation of specific abnormal calcium signals in the hippocampal CA1 and primary cortex M1 alleviates the progression of temporal lobe epilepsy

Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.

Spectral Properties and Sensitization of Ce^(3+) and Eu^(2+) Codoped Calcium Zinc Chlorosilicate

The Ce^3+ and Eu^2+ ions codoped calcium zinc chlorosilicate Ca_8Zn(SiO_4)_4Cl_2 phosphors have been synthesized for the first time. The diffuse reflection, excitation and emission spectra of Ca_8Zn(SiO_4)_4Cl_2∶Ce^3+, Eu^2+ have been measured at room temperature. The luminescence sensitizaiton of Eu^2+ by Ce^3+ inCa_8Zn(SiO_4)_4Cl_2∶Ce^3+, Eu^2+ has been expounded under the excitation of ultraviolet light and the efficient nonradiative energy transfer from Ce^3+ to Eu^2+ in this system is confirmed.

Elevated extracellular calcium ions accelerate the proliferation and migration of HepG2 cells and decrease cisplatin sensitivity

Hepatoblastoma is the most frequent liver malignancy in children.HepG2 has been discovered as a hepatoblastoma-derived cell line and tends to form clumps in culture.Intriguingly,we observed that the addition of calcium ions reduced cell clumping and disassociated HepG2 cells.The calcium signal is in connection with a series of processes critical in the tumorigenesis.Here,we demonstrated that extracellular calcium ions induced morphological changes and enhanced the epithelial-mesenchymal transition in HepG2 cells.Mechanistically,calcium ions promoted HepG2 proliferation and migration by up-regulating the phosphorylation levels of focal adhesion kinase(FAK),protein kinase B,and p38 mitogen-activated protein kinase.The inhibitor of FAK or Ca2+/calmodulin-dependent kinaseⅡ(CaMKⅡ)reversed the Ca2+-induced effects on HepG2 cells,including cell proliferation and migration,epithelial-mesenchymal transition protein expression levels,and phosphorylation levels of FAK and protein kinase B.Moreover,calcium ions decreased HepG2 cells'sensitivity to cisplatin.Furthermore,we found that the expression levels of FAK and CaMKⅡwere increased in hepatoblastoma.The group with high expression levels of FAK and CaMKⅡexhibited significantly lower ImmunoScore as well as CD8+T and NK cells.The expression of CaMKⅡwas positively correlated with that of PDCD1 and LAG3.Correspondingly,the expression of FAK was negatively correlated with that of TNFSF9,TNFRSF4,and TNFRSF18.Collectively,extracellular calcium accelerates HepG2 cell proliferation and migration via FAK and CaMKⅡand enhances cisplatin resistance.FAK and CaMKⅡshape immune cell infiltration and responses in tumor microenvironments,thereby serving as potential targets for hepatoblastoma.

水溶液环境下手性配合物Phe·Ca^(2+)对映异构机理的DFT研究

采用DFT(density functional theory)的M06-2X、MN15方法和处理溶剂效应的SMD模型方法,研究了水溶液中S-苯丙氨酸(S-Phe)与二价钙(Ca^(2+))配合物(Phe·Ca^(2+))的对映异构。反应通道研究发现,S-Phe·Ca^(2+)的对映异构可在质子以N和O分别为桥以及O和N联合为桥迁移的3个通道上实现。计算表明:最优势通道是质子以N为桥迁移,隐性水溶剂效应下决速步自由能垒是227.5 kJ/mol,显性水溶剂效应下该能垒降至108.0~117.6 kJ/mol。结果表明:水溶液中手性Phe·Ca^(2+)的消旋过程十分缓慢,将其用于生命体同补苯丙氨酸和钙元素可能比较安全。

Fura-2荧光探针研究Ca^(2+)对大肠杆菌细胞的跨膜作用

以Fura 2 /AM作为荧光探针 ,研究了Ca2 + 对大肠杆菌HB10 1细胞的跨膜作用 .考察了不同浓度外源钙离子处理不同生长时期细胞的跨膜行为 ,并采用停流技术测定了荧光动力学 .结果表明大肠杆菌在用CaCl2 溶液处理后 ,胞外Ca2 + 可大量进入胞内 ,且进入细胞的钙离子量与胞外钙离子浓度相关 ;处于对数生长前期的细胞与对数生长后期和稳定期的细胞相比 ,胞内自身Ca2 + 浓度低 ,但其摄取外源Ca2 + 的能力最强 ,这应该与其生理代谢活性是相关的 ,而且这一时期是大肠杆菌细胞最易建立人工诱导感受态的时期 .该研究对于测定革兰氏阴性菌细胞内Ca2 + 浓度及胞外离子的跨膜传导行为 。

微波辐照对离体淋巴细胞Ca^（2＋）浓度及Ca^（2＋）、Mg^（2＋）－ATP酶活力的影响

以２４５０ＭＨｚ连续微波辐照ＢＡＢＬ／Ｃ，小鼠离体淋巴细胞１５ｍｉｎ，３０ｍｉｎ，６０ｍｉｎ．结果发现０．５ｍｗ·ｃｍ－２组细胞内Ｃａ浓度明显下降，５和５０ｍＷ·ｃｍ－２组辐照３０ｍｉｎ后，细胞内Ｃａ２＋明显超载，并且表现出与质膜ｃａ２＋、Ｍｇ２＋－ＡＴＰ酶活性变化明显相关．ＤＮＡ合成结果提示，细胞内高ｃａ２＋可抑制细胞ＤＮＡ合成。

Ca^(2+)对磁黄铁矿浮选的“屏蔽效应”

以磁黄铁矿纯矿物为研究对象,采用SEM-EDS、ICP和XPS等分析方法,研究了矿浆中Ca^(2+)对磁黄铁矿可浮性的影响,并分析了其产生机制。对比普通水体和高钙水体中磁黄铁矿的浮选效果,发现高钙水体中磁黄铁矿回收率降低了14个百分点。通过多种检测分析手段证明Ca^(2+)能够在磁黄铁矿被氧化后的表面上形成一层CaSO_4薄膜,这层亲水薄膜极大地阻碍了CuSO_4对磁黄铁矿的活化,进而导致难以在高钙水体中浮选磁黄铁矿。

应用Fura－2／AM和Probenecid测定免疫细胞胞浆游离Ca^（2＋）浓度

人Ｂ细胞系Ｒａｊｉ和ＭΦ系Ｕ９３７细胞可将负载于胞内的Ｃａ￣（２＋）荧光示踪剂Ｆｕｒａ－２外排和房室化，质膜有机阴离子转运系统抑制剂Ｐｒｏｂｅｎｅｃｉｄ能阻断这些过程，而且对细胞Ｃａ￣（２＋）应答无不良影响。提示Ｒａｊｉ和Ｕ９３７细胞质膜上具有Ｆｕｒａ－２的转运系统；Ｐｒｏｂｅｎｅｃｉｄ可作为应用Ｆｕｒａ－２／ＡＭ研究这些细胞Ｇ２￣（２＋）应答的试剂。

爱大霉素和庆大霉素对胞浆Ca^(2+)影响的初步机制

目的 :探讨爱大霉素 (EM )和庆大霉素 (GM )对胞浆Ca2 +影响的初步机制。方法 :以Fura -2/AM为探针测定EM和GM在不同浓度时对LLC -PK1肾上皮细胞胞浆Ca2 +的影响 ,同位素示踪法测定EM和GM对线粒体Ca2 +摄取和内质网Ca2 +摄取的影响。结果 :EM和GM在1mmol/L时对胞浆Ca2 +浓度无显著影响 (P>0 05) ;在10mmol/L时可使胞浆Ca2 +显著上升 (P<0 01)。EM和GM在1mmol/L时显著促进线粒体Ca2 +摄取 (P<0 05) ;在10mmol/L时 ,二者显著抑制线粒体Ca2 +摄取。EM和GM在>3 4×10-1mmol/L时显著抑制内质网Ca2 +摄取 (P<0 05或P<0 01)。结论 :低浓度EM和GM未能引起胞浆Ca2 +升高 ,可能与其促进线粒体Ca2 +摄取与抑制内质网Ca2 +摄取相互平衡有关 ;高浓度EM和GM引起胞浆Ca2 +升高 ,可能与其均抑制线粒体和内质网Ca2

褪黑素对谷氨酸所致大鼠神经细胞Ca^(2+)内流的影响

目的 :研究褪黑素对谷氨酸引起的神经细胞Ca2 +内流的抑制作用。方法 :用Ca2 +敏感荧光指示剂Fura -2/AM负载大鼠脑细胞 ,测定神经细胞内游离Ca2 +浓度。结果 :谷氨酸500μmol/L可促进Ca2 +内流 ,显著增加细胞内游离Ca2 +浓度 (P<0. 01) ;应用褪黑素10 -5mol/L后可显著抑制Ca2 +内流 ,降低细胞内游离Ca2 +浓度 (P<0. 01)。结论 :褪黑素可通过抑制谷氨酸引起的Ca2 +内流保护神经细胞。

Wnt/Ca^(2+)信号通路在肢体缺血/再灌注损伤机制中的研究进展

Wnt/Ca^(2+)信号通路属于Wnt非经典通路,该通路的失调与细胞调亡、炎症反应等病理改变,以及许多疾病的发生、发展、转归有着密切联系。肢体缺血/再灌注损伤(LIRI)是临床工作中常遇到的一类难题,而Wnt/Ca^(2+)通路可诱使细胞内Ca^(2+)浓度升高并可活化Ca^(2+)敏感信号成分,其介导的细胞凋亡、Ca^(2+)超载和机体炎症等反应在LIRI中扮演重要角色。该文就Wnt/Ca^(2+)信号通路在LIRI病机中所起的作用进行综述。

Ca^(2+)对PHA促淋巴细胞分裂作用的影响

以小鼠脾淋巴细胞为实验材料,采用MTT微量自动比色法判断细胞分裂状况,观察PHA的促淋巴细胞分裂作用时Ca^(2+)的影响。结果发现:加Ca^(2+)的最大刺激组的光密度(OD)值比对照组提高了35.4％,Ca^(2+)的最大刺激浓度为4％葡萄糖酸钙.结果表明Ca^(2+)有增强PHA的有丝分裂原作用,并且存在明显的量—效关系。

Roles of Na^+/Ca^(2+) exchanger 1 in digestive system physiology and pathophysiology

The Na^+/Ca^(2+) exchanger(NCX) protein family is a part of the cation/Ca^(2+) exchanger superfamily and participates in the regulation of cellular Ca^(2+) homeostasis. NCX1, the most important subtype in the NCX family, is expressed widely in various organs and tissues in mammals and plays an especially important role in the physiological and pathological processes of nerves and the cardiovascular system. In the past few years, the function of NCX1 in the digestive system has received increasing attention; NCX1 not only participates in the healing process of gastric ulcer and gastric mucosal injury but also mediates the development of digestive cancer, acute pancreatitis, and intestinal absorption.This review aims to explore the roles of NCX1 in digestive system physiology and pathophysiology in order to guide clinical treatments.

K+alkalization promoted Ca2+intercalation in V2CTx MXene for enhanced Li storage

Although MXenes is highly attractive as anode materials of lithium ion batteries,it sets a bottleneck for higher capacity of the V2CTxMXene due to the limited interlayer space and the derived surface terminations.Herein,the cation intercalation and ion-exchange were well employed to achieve a K+and Ca2+intercalated V2CTxMXene.A larger interlayer distance and low F surface terminations were thereof obtained,which accelerates the ion transport and promotes the delicate surface of V2CTx MXene.As a result,a package of enhanced capacity,rate performance and cyclability can be achieved.Furthermore,the ion exchange approach can be extended to other 2 D layered materials,and both the interlayer control and the surface modification will be achieved.

Ca^(2+) cytochemical changes of hepatotoxicity caused by halothane and sevoflurane in enzyme-induced hypoxic rats

AIM： To investigat the relation between hepatotoxicity of halothane and sevoflurane and altered hepatic calcium homeostasis in enzyme-induced hypoxic rats. METHODS： Forty-eight rats were pretreated with phenobarbital and randomly divided into six groups （eight in each group） and exposed to O2/N2/1.2 MAC anesthetics for 1 h： normal control （NC）, 21% O2/79% N2; hypoxic control （HC）, 14% O2/86% N2; normal sevoflurane （NS）, 21% O2/ N2/1.2MAC sevoflurane; hypoxic sevoflurane （HS）, 14% O2/N2/1.2MAC sevoflurane; normal halothane （NH）21%O2/79%N2/1.2MAC halothane; hypoxic halothane （HH）, 14%O2/N2/1.2MAC halothane. Liver specimens and blood were taken 24 h after exposure to calcium and determined by EDX microanalysis. RESULTS： The liver of all rats given halothane （14% O2） had extensive centrilobular necrosis and denaturation. Morphologic damage was accompanied with an increase in serum glutarnic pyruvic transminase. In groups NH and HH, more calcium was precipitated in cytoplasm and mitochondria. CONCLUSION： These results suggest that halothane increases cytosolic Ca^2＋ concentration in hepatocytes. Elevation in Ca^2＋ concentration is implicated in the mechanism of halothane-induced hepatotoxicity. sevoflurane is less effective in affecting hepatic calcium homeostasis than halothane.

Aluminum neurotoxicity effects on intracellular Ca^(2+) homeostasis in the rat cerebral cortex

Studies have suggested that aluminum, a neurotoxic metal, is involved in the progression of neurodegenerative diseases. Previous studies have confirmed that aluminum influences intracellular Ca^2＋ homeostasis. However, it remains unclear whether aluminum increases or decreases intracellular Ca^2＋ concentrations. The present study demonstrated that Al^3＋ competitively binds to calmodulin （CAM）, together with Ca^2＋, which resulted in loss of capacity of CaM to bind to Ca^2＋, leading to increased [Ca^2＋]i. Al^3＋ stimulated voltage-gated calcium channels on cell membranes, which allowed a small quantity of Ca^2＋ into the cells. Al^3＋ also promoted calcium release from organelles by stimulating L-Ca^2＋αlc to trigger calcium-induced calcium release. Although Al^3＋ upregulated expression of Na＋/Ca^2＋exchanger mRNA, increased levels of Ca^2＋ and Na＋/Ca^2＋ exchanger did not maintain a normal Ca^2＋ balance. Al^3＋ resulted in disordered intracellular calcium homeostasis by affecting calcium channels, calcium buffering, and calcium expulsion.

抑制IP3R-Ca^(2+)途径对对乙酰氨基酚所致肝损伤及其线粒体内质网结构偶联的影响

目的探讨抑制肌醇-1,4,5-三磷酸受体(IP3R)-Ca^(2+)途径对对乙酰氨基酚(APAP)所致肝损伤及其线粒体内质网结构偶联(MAMs)的影响。方法40只SPF级雄性C57BL/6小鼠随机分为正常对照组、模型组、IP3R抑制剂(2-APB)组、钙离子螯合剂(BAPTA-AM)组,每组10只。模型组、2-APB组、BAPTA-AM组单次腹腔注射APAP(300 mg/kg)。注射APAP前30 min,2-APB组腹腔注射2-APB(20 mg/kg),BAPTA-AM组腹腔注射BAPTA-AM(2.5 mg/kg)。腹腔注射APAP 24 h后处死各组小鼠。测定血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平;HE染色观察肝脏病理变化;透射电镜观察肝细胞中线粒体、内质网结构及MAMs变化;测定肝组织匀浆中的Ca^(2+)水平;Western blot测定肝组织中线粒体融合蛋白1(MFN1)、线粒体融合蛋白2(MFN2)、1,4,5-三磷酸肌醇受体1(IP3R1)、葡萄糖调节蛋白75(GRP75)蛋白表达水平。结果与正常对照组相比,模型组小鼠血清ALT及AST水平有所升高(P<0.01),肝脏组织病理学可见肝细胞排列紊乱,并出现肝细胞变性、小叶中心性坏死;透射电镜示线粒体嵴断裂、消失,内质网肿胀断裂,MAMs数量增加;肝组织匀浆中Ca^(2+)含量增加(P<0.01);MFN1、MFN2蛋白表达降低(P<0.01),IP3R1及GRP75蛋白表达增加(P<0.01)。与模型组相比,2-APB组和BAPTA-AM组小鼠血清ALT、AST水平下降(P<0.01),肝脏病理变化明显改善,MAMs减少,肝组织匀浆中Ca^(2+)含量减少(P<0.01),MFN1、MFN2的蛋白表达水平上调(P<0.01),IP3R1及GRP75蛋白表达降低(P<0.01)。结论抑制IP3R-Ca^(2+)途径可以保护APAP所致的肝损伤,其机制与降低肝脏Ca^(2+)水平、减少MAMs数量、调节MAMs相关蛋白的表达有关。

The effect of external Ca^(2+) and Ca^(2+)-channel modulators on red-light-induced swelling of protoplasts of Phaseolus radiatus L.

Red-light-induced swelling of the protoplasts isolated from hypocotyl of etiolated mung bean (Phaseolus radiatus L.) was observed only when Ca2+ ions were present in the medium. The optimal CaCl2 concentration was 250 μM. Swelling response declined when Ca2+ was supplied into the medium after red light irradiation. The Ca2+-chelator EGTA eliminated the red-light-induced swelling and 45Ca2+ accumulation in the protoplasts. In contrast, A23187, a Ca2+-ionophore, could mimic the effect of red light in darkness. These results indicate that Ca2+ may play a role in light signal transduction. In addition, swelling response was prevented by TFP and CPZ (both are CaM antagonists), implying the involvement of CaM in red-light-induced and Ca2+ -dependent protoplast swelling.

火焰原子吸收分光光度法测定海藻酸钙敷料中Ca^(2+)、Na^+、Fe^(3+)离子含量

目的:建立海藻酸钙敷料中钙、铁、钠离子含量的测定方法。方法:以镧溶液为释放剂,采用火焰原子吸收分光光度法定量测定海藻酸钙敷料中Ca2+离子及Na+、Fe3+离子含量。结果:Ca2+、Na+、Fe3+离子的线性范围2.0μg/mL^10.0μg/mL(r=0.9999),0.1μg/mL^0.5μg/mL(r=0.9996),3.0μg/mL^7.0μg/mL(r=0.9996);加样回收率(n=6)分别为102%,99.0%,97.5%,RSD分别为2.5%,2.1%,1.2%。结论:该方法准确、可靠,重复性良好,可用于海藻酸钙敷料中钙、铁、钠离子含量的测定。

Relation between Neodymium and Calcium in Rape under Ca-Deficiency

The function of Nd^(3+) with different concentrations in oilseed rape under Ca-deficiency was studied. The results indicate that the root surface-area of rape which treated with 3 μmol·L^(-1) Nd(NO_3)_3 is enlarged, and the taproot length, root dry weight and root CEC all increase as well as roots oxidizing capacity. Nd^(3+) can replace Ca^(2+) partially, and the replacement action is embodied likely through plasmolemma Ca^(2+)-ATPase with signal transduction pathway. Nd^(3+) shows mainly its toxic action under high concentration (60 μmol·L^(-1)).