卡托普利和依那普利拉对分离的大鼠心肌细胞内游离Ca^2＋浓度的影响

目的：研究转换酶抑制剂卡托普利（Ｃａｐ）和依那普利拉（Ｅｎａ）对ＳＨＲ和ＷＫＹ大鼠心肌细胞内游离Ｃａ＾２＋浓度的影响，方法：用荧光探针Ｆｕｒａ２－ＡＭ结合计算机图象处理技术测定分离心肌细胞内游离Ｃａ＾２＋浓度，结果：ＳＨＲ心理细胞内游离Ｃａ＾２＋浓度（１７４±５ｎｍｏｌ．Ｌ＾－１）较ＷＫＹ大鼠（１４８±１５ｎｍｏｌ．Ｌ＾－１）高（Ｐ〈０．０１），Ｃａｐ和Ｅｎａ能明显降低ＳＨＲ心肌细胞内游离Ｃａ＾２     

卡托普利对培养大鼠心肌细胞缺氧和复氧损伤的保护作用

应用细胞内微电极技术观察到卡托普利在４０ｍｇ．Ｌ＾－１浓度下能延长培养大鼠心肌细胞在缺氧环境中的搏动时间，减少搏劝服律失常的发生，部分纠正由复氧所致异常心肌细胞电活动参数，缓解心肌细胞复极后再次停搏的发生。     

卡托普利和依那普利拉对分离的大鼠心肌细胞内游离Ca~（2＋）浓度的影响

目的：研究转换酶抑制剂卡托普利（Ｃａｐ）和依那普利拉（Ｅｎａ）对ＳＨＲ和ＷＫＹ大鼠心肌细胞内游离Ｃａ２＋浓度的影响．方法：用荧光探针Ｆｕｒａ２ＡＭ结合计算机图象处理技术测定分离心肌细胞内游离Ｃａ２＋浓度．结果：ＳＨＲ心肌细胞内游离Ｃａ２＋浓度（１７４±５ｎｍｏｌ·Ｌ－１）较ＷＫＹ大鼠（１４８±１５ｎｍｏｌ·Ｌ－１）高（Ｐ＜００１）．Ｃａｐ和Ｅｎａ能明显降低ＳＨＲ心肌细胞内游离Ｃａ２＋浓度（分别为１６１±１１和１６６±７ｎｍｏｌ·Ｌ－１，Ｐ分别＜００５），但对ＷＫＹ的无影响（Ｐ＞００５）．两药均能明显降低ＮＥ和ＡｎｇＩ引起的ＳＨＲ和ＷＫＹ大鼠心肌细胞内Ｃａ２＋升高，同时也能明显降低ＫＣｌ引起的ＳＨＲ细胞内Ｃａ２＋升高（Ｐ＜００５），但对ＷＫＹ大鼠的无明显影响（Ｐ＞００５）．结论：Ｃａｐ和Ｅｎａ对病理性电压依赖性Ｃａ２＋通道有直接抑制作用．     

卡托普利和依那普利对血管平滑肌细胞内钙的影响

检测ＡＣＥ抑制剂对主动脉平滑肌细胞内Ｃａ＾２＋的影响。用荧光标计和图象处理技术。ＳＨＲ细胞内Ｃａ＾２＋以及ＫＣｌ，ＮＥ和Ａｎｇ在ＳＨＲ细胞引起的Ｃａ＾２＋增加多于ＷＫＹ细胞。Ｃａｐ和Ｅｎａ不影响ＫＣｌ     

吡那地尔预处理对缺氧/复氧成后年大鼠心肌细胞内钙离子浓度的影响

目的观察吡那地尔(Pinacidil)预处理对缺氧/复氧后成年大鼠心肌细胞内Ca2+浓度([Ca2+]i)的影响,以探讨吡那地尔在缺氧/复氧中抑制钙超载作用的机制。方法通过Langen-dorff离体心脏灌注装置,用Ⅱ型胶原酶对心脏逆行灌注,进行成年大鼠心肌细胞的分离与培养,建立心肌细胞缺氧/复氧模型。实验分组及处理:(1)正常组(NOR组):细胞正常培养;(2)缺氧/复氧组(CON组):细胞在95%N2+5%CO2培养箱中缺氧45 min,复氧1 h;(3)吡那地尔组(Pina组):先加入吡那地尔(30μmol/L)预处理15 min,再缺氧45 min,复氧1h;(4)格列苯脲拮抗Pina组(Gi+Pina组):先用格列苯脲(50μmol/L)处理5 min后,余处理同Pina组。通过Fluo-3/AM荧光指示剂负载,用激光共聚焦显微镜检测心肌细胞Ca2+浓度变化。结果 NOR组心肌细胞内钙离子荧光强度值较低;细胞缺氧45 min,复氧1 h后其荧光强度值与NOR组相比显著增高(P<0.01);而Pina组细胞内荧光强度值较CON组及Gi+Pina组低(P<0.01)。结论心肌细胞缺氧/复氧后...     

Verapamil和Mn~（2＋）对缺氧及缺氧复氧心肌细胞内pH的影响

采用荧光探针ＢＣＥＣＦ／ＡＭ结合计算机图像处理技术测定不同时间的缺氧和缺氧复氧单心肌细胞内ｐＨ的变化以及Ｃａ２＋通道阻滞剂Ｖｅｒａｐａｍｉｌ和Ｎａ＋－Ｃａ２＋交换抑制剂Ｍｎ２＋对其的影响。结果显示随着缺氧时间的延长，细胞内ｐＨ也逐渐降低。复氧开始４０ｍｉｎ内，细胞内ｐＨ并未恢复正常。Ｖｅｒａｐａｍｉｌ能减轻缺氧细胞内酸化程度并使其接近正常水平（Ｐ＞０．０５），却未能减轻缺氧复氧细胞内的酸化。无论是缺氧或缺氧复氧心肌细胞，Ｍｎ２＋均未能减轻细胞内的酸化程度。本实验结果提示缺氧和缺氧复氧时细胞内酸化途径并非完全一致。ＶｅｒａＰａｍｉｌ抑制缺氧细胞内ｐＨ下降是其保护缺氧心肌作用的机制之一。     

Verapamil和Mn~（2＋）对缺氧和复氧心肌细胞内Na~＋浓度的影响

采用荧光探针ＳＢＦＩ／ＡＭ结合计算机图像处理技术测定缺氧和复氧时单心肌细胞内Ｎａ＋的变化及钙通道阻滞剂Ｖｅｒａｐａｍｉｌ和Ｎａ＋－Ｃａ２＋交换抑制剂Ｍｎ２＋对其的影响。结果表明随缺氧和复氧时间的延长细胞内Ｎａ＋均增加。Ｖｅｒａｐａｍｉｌ对缺氧或复氧细胞内Ｎａ＋无影响（Ｐ＞０．０５），Ｍｎ２＋能使复氧细胞内Ｎａ＋含量增加（Ｐ＜０．０１）。本文推断Ｖｅｒａｐａｍｉｌ不是通过降低细胞内Ｎａ＋浓度而发挥保护心肌作用，特异性强的Ｎａ＋－Ｃａ２＋交换抑制剂会使复氧心肌细胞内Ｎａ＋含量增加而削弱其保护作用。     

卡托普利对培养大鼠心肌细胞缺氧和复氧损伤的保护作用

应用细胞内微电极技术观察列卡托普利(captopril, Cap)在40mg·L~(-1)浓度下能延长培养大鼠心肌细胞在缺氧环境中的搏动时间,减少搏动节律失常的发生。部分纠正由复氧所致异常心肌细胞电活动参数,缓解心肌细胞复极后再次停搏的发生,     

卡托普利和西卡普鲁斯特对心肌细胞膜流动性及脂质过氧化的保护作用

研究的主要目的旨在探讨卡托普利和西卡普鲁斯特对培养新生乳鼠心肌细胞缺氧缺糖时膜流动性改变的保护作用。为了探讨其它与膜相关的改变，我们同时观察了培养细胞缺氧时脂质过氧化水平及乳酸脱氢酶（LDH）的释放情况。采用荧光分光光度计测定稳态荧光各向异性（rs）的改变来监测膜流动性，脂质过氧化水平通过测定硫代巴比妥酸反应物（简称TBARS）含量来评估，实验表明卡托普利（180μmol/L）、西卡普鲁斯特（30nmol/L）和消炎痛（1μmol/L）对正常新生乳鼠心肌细胞的rs值、TBARS水平及LDH活性均无影响，卡托普利和西卡普鲁斯特均能显著阻止缺氧缺糖所心肌细胞rs值、TBARS含量和LDH释放的增加，且 均有剂量依赖性，消炎痛能取消卡托普利对TBARS产生及LDH释放的作用，但是仍保留膜流动性的保护作用。这些结果说明卡托普利和西卡普鲁斯特具有保护心肌细胞缺氧损伤时膜流动性和脂质过氧化的作用。卡托普利的保护作用可能是通过促进前列环素的合成和／或释放介导的。     

Alpha 1-adrenoceptor stimulation increases intracellular pH and Ca2+ in cardiomyocytes through Na+/H+ and Na+/Ca2+ exchange

The effects of alpha 1-adrenergic stimulation on intracellular pH (pHi) and Ca2+ concentration ([Ca2+]i) were investigated in isolated rat cardiomyocytes with fluorescence dyes, BCECF and fura-2, respectively. In the presence of 5 or 25 mM HCO3- norepinephrine (NE) increased pHi in a dose-dependent manner. Intracellular alkalinization was inhibited by prazosin and phentolamine but not by yohimbine. NE-induced alkalinization was inhibited in the presence of a Na+/H+ exchange inhibitor (5-(N,N-hexamethylene) amiloride (HMA)), a C kinase inhibitor (H-7) or a calmodulin inhibitor (W-7), or in the absence of extracellular Na+. NE also increased [Ca2+]i following the pHi increase, which was abolished in the absence of extracellular Na+ or Ca2+. This Ca2+ influx was inhibited by HMA but not by diltiazem (10(-5) M). Thus, we conclude that alpha 1-adrenergic stimulation enhances Na+/H+ exchange by activation of C kinase, thereby allowing intracellular alkalinization, and that subsequent activation of Na+/Ca2+ exchange increases Ca2+ influx.     

复合离子盐对老年人细胞内Na+、K+、Ca2+的影响及其机制

目的：观察复合离子盐对老年人细胞内Na^＋、K^＋、Ca^2＋及红细胞膜钠泵和钙泵活性的影响。方法：在天津市河东区社区中抽取226例老年人作为研究对象．其中高血压者112例。正常血压者114例。两者再随机分为离子盐组和普通加碘盐组．分别给予复合离子盐和普通加碘盐摄入，6个月后观察研究对象细胞内Na^＋、K^＋、Ca^2＋及钠泵、钙泵活性的变化。结果：6个月时高血压患者中离子盐组细胞内钠、钙离子浓度低于基线水平（P〈0．05），但钾离子无明显变化。离子盐组钠泵、钙泵活性均明显高于基线水平（P〈0．05），但在正常血压者中，2组与基线水平比较差异无统计学意义。结论：复合离子盐可增强钠泵、钙泵活性，使细胞内的钠、钙含量减少。     

Effect of dronedarone on Na+, Ca2+ and HCN channels

Previous studies showed that amiodarone causes state-dependent inhibition of Na(+) channels thereby mediating an atrial-selective drug effect. The aim of the present study was to investigate the impact of the new antiarrhythmic compound dronedarone on Na(+), Ca(2+) and hyperpolarization-activated cyclic nucleotide-gated ion channels. Monophasic action potentials (MAP) and effective refractory period (ERP) were studied in arterially perfused left atria and ventricular wedge preparations of the pig. Fast Na(+) and Ca(2+) currents in isolated guinea pig ventricular myocytes as well as human HCN4 channels expressed in Chinese hamster ovary (CHO) cells were investigated with the patch-clamp technique. In left atrial epicardial tissue, dronedarone (3?μM) had no effect on the MAP duration, but the drug caused a significant prolongation of the ERP from 145?±?9 to 184?±?17?ms (n?=?6; p?相似文献   

Effects of SEA0400 and KB-R7943 on Na+/Ca2+ exchange current and L-type Ca2+ current in canine ventricular cardiomyocytes

SEA0400 and KB-R7943 are compounds synthesised to block transsarcolemmal Na⁺/Ca²⁺ exchange current (I_Na/Ca); however, they Have also been shown to inhibit L-type Ca²⁺ current (I_Ca). The potential value of these compounds depends critically on their relative selectivity for I_Na/Ca over I_Ca. In the present work, therefore, the concentration-dependent effects of SEA0400 and KB-R7943 on I_Na/Ca and I_Ca were studied and compared in canine ventricular cardiomyocytes using the whole-cell configuration of the patch clamp technique. SEA0400 and KB-R7943 decreased I_Na/Ca in a concentration-dependent manner, having EC₅₀ values of 111±43 nM and 3.35±0.82 M, when suppressing inward currents, while the respective EC₅₀ values were estimated at 108±18 nM and 4.74±0.69 M in the case of outward current block. SEA0400 and KB-R7943 also blocked I_Ca, having comparable EC₅₀ values (3.6 M and 3.2 M, respectively). At higher concentrations (10 M) both drugs accelerated inactivation of I_Ca, retarded recovery from inactivation and shifted the voltage dependence of inactivation towards more negative voltages. The voltage dependence of activation was slightly modified by SEA0400, but not by KB-R7943. Based on the relatively good selectivity of submicromolar concentrations of SEA0400—but not KB-R7943—for I_Na/Ca over I_Ca, SEA0400 appears to be a suitable tool to study the role of I_Na/Ca in Ca²⁺ handling in canine cardiac cells. At concentrations higher than 1 M, however, I_Ca is progressively suppressed by the compound.     

Complex formation of lithium hydroxybutyrate with ions of Na+, K+, Ba2+, Mg2+, and Ca2+

The interaction of lithium hydrobutyrate (LiR) with ions of Na+, K+, Ba2+, Mg2+ and Ca2+ was studied. The coordination is implemented by atoms of oxygen of the carboxyl group. R forms the most stable complexes with ions of Mg2+ and Ca2+. Complexes of CaR+ and CaR2 types are formed with ions of Mg2+ and Ca2+. For LiR complex the logarithm of stability constant (lg K) is 0.7 +/- 0.3, for CaR+ - 2.0 +/- 0.2 and for CaR2 - 0.2 +/- 0.3. The interaction of lithium hydroxybutyrate with ions of Ca2+ and Mg2+ may be of great importance in the mechanism of its cardiotropic effect.     

Effects of Mg2+, Mn2+ and Ca2+ on adenylcyclase activity

Summary In membrane preparations from immature erythrocytes from rats the effects of the divalent cations Mg²⁺, Mn²⁺ and Ca²⁺ on basal activity of adenylcyclase as well as on enzyme activity stimulated by isoprenaline (Ipn) or guanylyl-imidodiphosphate [Gpp(NH)p] were investigated. — Mn²⁺ is a ten-fold stronger activator of the enzyme than Mg²⁺ irrespective of the stimulant used. At suboptimal concentrations of the cations at all concentrations of Gpp(NH)p used (10^–6 to 10^–3M) reaction velocities increase progressively over an incubation period of 40 min. Optimal cation concentrations, however, i.e. 3×10^–3M Mn²⁺ and 3×10^–2M Mg²⁺ elicit a constant and at 10^–4M Gpp(NH)p maximal reaction velocity.In contrast, the Ipn-stimulated cAMP synthesis proceeds linearly at all Ipn concentrations used; a change of cation concentrations elicits only a change in reaction velocity, which is maximal at 10^–3M Mn²⁺ and 10^–2M Mg²⁺ respectively. — Ca²⁺ inhibits adenylcyclase activity in a non-competitive manner, irrespective of the stimulant and ion concentration used. The Mg²⁺-activated enzyme, however, is more susceptible to the inhibiting effect of Ca²⁺ than the Mn²⁺-activated enzyme. — It is concluded that Mn²⁺ and Mg²⁺ are allosteric effectors of the enzyme adenylcyclase, acting at a Me²⁺-site of the catalytic unit of adenylcyclase.This study was supported by the Deutsche Forschungsgemeinschaft. Preliminary accounts were presented at the 17. Spring Meeting of the Deutsche Pharmakologische Gesellschaft (Wiemer et al., 1976)     

原子吸收光谱法同时测定人工肾透析液中钾、钠、钙、镁含量

目的 :探索同时测定人工肾透析液中的钾、钠、钙、镁含量的方法。方法 :采用原子吸收火焰法 (AAS) ,加入 4 g·L-1SrCl2 作为K+ 、Na+ 的离子抑制剂和Ca2 + 、Mg2 + 的离子释放剂 ,选择K+ 76 9.5nm、Na+ 330 .2nm、Ca2 + 4 2 2 .7nm、Mg2 + 2 85 .2nm作为分析线进行测定。结果 :方法平均回收率分别为 :K+ 98.7% ,Na+ 99.9% ,Ca2 + 10 0 .7% ,Mg2 + 99.7% ;精密度为 :K+0 .5 5 %～ 1.0 0 % ,Na+ 0 .30 %～ 0 .5 1% ,Ca2 + 0 .6 2 %～ 0 .87% ,Mg2 + 1.0 1%～ 1.4 0 %。结论 :方法快速 ,准确可靠 ,可满足人工肾透析液中K+ 、Na+ 、Ca2 + 、Mg2 + 的快速测定。     

Effects of a Lasiodora spider venom on Ca2+ and Na+ channels.

The venom of a Brazilian spider, Lasiodora sp (Mygalomorphae, Theraphosidae), was screened for activity against ion channels using Ca2+ imaging and whole-cell patch clamp in GH3 cells. When tetrodotoxin (TTX) was present to block Na+ channels, the venom abolished the Ca2+ oscillations that are normally present in these cells and reduced the basal level of intracellular Ca2+. Under patch clamp, the venom reduced the L-type Ca2+ channel conductance and caused a positive shift in its voltage dependence of activation. In addition to these effects, when applied without TTX, the venom also caused a slow and noisy increase in intracellular Ca2+. The sensitivity of this second effect to TTX suggested an effect on Na+ channels, which was tested using patch clamp. Control Na+ currents inactivated completely as a single exponential. Treatment with the venom did not affect the amplitude of I(Na), but caused it to divide in two slower exponential components plus a sustained component, all of which were suppressed by TTX. The venom also caused a negative shift in the voltage dependence of activation and steady-state inactivation of I(Na). The observed effects of this venom on whole-cell currents explain the changes it causes in intracellular Ca2+ in GH3 cells and demonstrate that the venom of this spider is a source of toxins active against ion channels.