Puerarin blocks Na~+ current in rat ventricular myocytes

AIM: To study the effect of puerarin (Pue) on Na~+ channel in rat ventricular myocytes. METHODS: Whole-cell patch-clamp technique was applied on isolated cardiomyocytes from rats. RESULTS: Pue inhibited cardiac I_(Na) in a positive rate-dependent and dose-dependent manner, with an IC_(50) of 349 μmol/L. The kinetics of blockage of cardiac sodium channel by Pue resembled the ClassIa/Ic of antiarrhythmic agents. Pue 300 μmol/L did not alter the shape of the I-V curve of I_(Na), but markedly shifted the steady-state inactivation curve of I_(Na) towards more negative potential by 15.9 mV, and postponed the recovery of I_(Na) inactivation state from (21.9±1.6) ms to (54.4±3.4) ms (P<0.01 ). It demonstrated that the steady state of inactivation was affected by Pue significantly. CONCLUSION: Pue protected ventricular myocytes against cardiac damage and arrhythmias by inhibiting recovery from inactivation of cardiac Na~+ channels.     

环维黄杨星D延长大鼠心室肌细胞APD作用的分子机制研究

目的　研究环维黄杨星D对分离的大鼠心室肌细胞内向整流钾电流 (IK1 )、瞬时外向钾电流 (Ito)、L 型钙电流(ICa L)和动作电位时程 (APD)的影响。方法　采用全细胞膜片钳技术记录大鼠心室肌细胞IK1 、Ito、ICa L 和APD。结果　 1和10 μmol·L- 1 环维黄杨星D明显延长分离大鼠心室肌细胞APD50 和APD90 ,10 μmol·L- 1 可明显降低静息膜电位 (RP)。环维黄杨星D对IK1 内向电流和外向电流均有明显抑制作用 ,当指令电压为 - 10 0mV时 ,1和 10 μmol·L- 1 环维黄杨星D分别使IK1 电流密度从给药前的 ( - 8.0± 1.1)pA pF降至 ( - 4 .1± 0 .7)pA pF和 ( - 3.4± 0 .8)pA pF ;当指令电压 - 30mV时 ,分别使IK1 电流密度从 ( 1.10± 0 .2 4 )pA pF降至 ( 0 .6 1± 0 .18)pA pF和 ( 0 .36± 0 .11)pA pF ;在钳制电位从 0到 + 6 0mV之间 ,环维黄杨星D明显抑制Ito,当指令电压 4 0mV时 ,1和 10 μmol·L- 1 环维黄杨星D分别使Ito电流密度从给药前的 ( 8.9± 2 .0 )pA pF降至 ( 5 .5± 1.2 )pA pF和 ( 4 .9± 0 .9)pA pF。环维黄杨星D浓度依赖性抑制ICa L,在指令电压为 10mV时 ,1和 10 μmol·L- 1 分别使ICa L电流密度从给药前的 ( - 9.9± 1.8)pA pF降至 ( - 6 .4± 1.4 )pA pF和 ( - 4 .2± 0 .6 )pA pF。结论　环     

Veratridine modifies the TTX-resistant Na channels in rat vagal afferent neurons

A number of neurotoxins from venoms of invertebrates and plants are ligands for voltage-gated Na⁺ channels and are useful tools for studying Na⁺ channel function and structure. Using whole-cell recordings from vagal afferent nodose neurons, we studied neurotoxins that target Na⁺ channels. We asked whether Ts3 (an α-scorpion toxin) and/or veratridine (a lipid-soluble toxin), could modify the TTX-resistant Na⁺ current generated by vagal afferent nodose neurons. Nodose TTX-resistant current was not affected by Ts3, whereas Ts3 slowed inactivation of the current generated by TTX-sensitive current component. We found that veratridine inhibited the TTX-resistant Na⁺ currents on rat nodose neurons. Interestingly, veratridine-modified Na⁺ channels developed a persistent current that accounted for the large tail current observed. We propose that veratridine modifies TTX-resistant Na⁺ channels through a mechanism distinct from its actions on other voltage-gated Na⁺ channels.     

N-甲基-D-天门冬氨酸受体及其调控的钙内流在大鼠感染性脑损伤中的变化

为探讨Ｎ－甲基－Ｄ－天门冬氨酸（ＮＭＤＡ）受体及其调控的钙内流在感染性脑损伤发病机制中的作用，采用Ｆｕｒａ－２／Ａｍ荧光法检测大鼠大脑皮质突触体内游离钙浓度（［Ｃａ＋＋］ｉ）。结果表明，注射百日咳杆菌组的［Ｃａ＋＋］ｉ较对照组显著增加（Ｐ均＜０．０１），并与注菌时间呈正相关关系（４小时ｖｓ０．５小时和２４小时ｖｓ４小时，Ｐ＜０．０５和＜０．０１）。ＮＭＤＡ受体的非竞争性拮抗剂ＭＫ－８０１预处理组（ＭＢＰ）的［Ｃａ＋＋］ｉ、脑含水量和伊文思蓝含量均较注菌组显著减少（Ｆ值分别为７２．２５、１６．８９、１４．３６，Ｐ＜０．０１和＜０．０５），并以２４小时［Ｃａ＋＋］ｉ减少最为明显（Ｐ＜０．０１）。提示ＮＭＤＡ受体调控的神经元内钙超载在感染性脑损伤、尤其在迟发性脑损伤的发病机制中起着重要作用。     

声测胆经体表循行线的实验研究

足少阳胆经，多弯多折，循行线长，检测难度较大。本文用低频输声的方法对３９名健康学生进行了右侧胆经的全程检测，循经性波出现率达到７２．７３％～９０．００％。再次证实了低频声波具有循本经经线传导的特异性，其传导轨迹与古典描述的胆经经线十分一致，并客观证实了胆经走行中５处弯曲的存在，同时也证实了胆经与三焦经、肝经的衔接，显示了经络是声的良导路     

T型钙通道在心肌肥厚大鼠心肌细胞钙内流中的作用

目的研究T型钙通道在心肌细胞钙离子内流中的作用及其对心脏兴奋收缩耦联的可能影响。方法测定选择性T型钙通道阻滞剂米贝拉地尔对培养的SD乳大鼠心室肌细胞和二肾一夹心肌肥厚大鼠心室肌细胞[Ca2+]i的影响。结果血管紧张素Ⅱ(AngⅡ)刺激使乳大鼠心室肌舒张期细胞[Ca2+]i增高,收缩期细胞[Ca2+]i降低,[Ca2+]i上升和下降的时间延长。米贝拉地尔1.25～5μmol·L-1浓度依赖性降低AngⅡ引起的细胞[Ca2+]i变化。在心肌肥厚模型大鼠,咖啡因刺激后,[Ca2+]i增幅和最高[Ca2+]i明显降低。而米贝拉地尔25mg·kg-1·d-1(灌胃给药7～9周)组加入咖啡因刺激后细胞内[Ca2+]i增幅和最高[Ca2+]i明显增高。结论T型钙通道异常开放可以引起心肌细胞内钙超载。阻断T型钙通道,可能通过改善肌浆网摄取及释放钙的功能而抑制心肌细胞钙超载。     

The interactions of phenytoin and its binding site in DI‐S6 segment of Na+ channel voltage‐gated peptide by NMR spectroscopy and molecular modeling study

Abstract: Nuclear magnetic resonance (NMR) spectra of a model peptide (BL‐DIS6), in the presence of anticonvulsant diphenyl drug, phenytoin (DPH), were measured to obtain the interactions between the selected drug and the model peptide. BL‐DIS6's sequence corresponds to the S6 segment in domain I of rat brain type IIA Na⁺‐channel. NMR studies have demonstrated that the magnitude of the chemical shifts of amide‐ and α‐protons can be used as a measurement of the complex stability and binding site of the peptide. Our NMR results propose a 3₁₀‐helical structure for BL‐DIS6, and suggest a binding cavity for DPH that involves the hydrophobic particles of residues Ans‐7, Leu‐8, Val‐11, and Val‐12. Furthermore, molecular modeling was performed to provide a possible complex conformation that the phenyl portion of DPH is accommodated in the proximity of the C‐terminal residues Ala‐11 and Val‐12, and simultaneously the heterocyclic amine ring of DPH is perching at the residue Asn‐7 periphery and stabilizing the phenyl portion deep insertion into the peptide.     

Cytochrome P450 epoxygenases as EDHF synthase(s)

The metabolism of arachidonic acid by cytochrome P450 (CYP) epoxygenases generates epoxyeicosatrienoic acids (EETs) which affect numerous cellular process including Ca(2+) signaling and the activity of Ca(2+)-dependent K(+) channels. The expression of the CYP epoxygenase(s) that generate EETs in endothelial cells is not constitutive but is determined by a number of physical (fluid shear stress and cyclic stretch) and pharmacological stimuli which also affect responses attributed to an endothelium-derived hyperpolarizing factor (EDHF). This review summarizes the role played by EETs, and the enzymes that generate and metabolize them, in EDHF-mediated responses.     

Downregulation of Kυ4.2 and Kυ4.3 channel gene expression in right ventricular hypertrophy induced by monocrotaline in rat

INTRODUCTION The calcium-independent transient outward potas-sium current (Ito) is activated by depolarization and playsa key role in controlling the amplitudes and cardiac ac-tion potential duration (APD). Ito contributesto the phase1 repolarization of action potential in myocytes, theprolongation of APD is the result of decrease in Ito den-sity[1]. Ito which is encoded by genes of Kv1.4, Kv4.2,and Kv4.3[2], based on differences in kinetics, as wellas recovery from inactivation…     

化淤通络胶囊对气虚血淤脑缺血大鼠血液流变学的影响

目的 观察化淤通络胶囊对气虚血淤缺血性中风大鼠模型血液流变学的影响.方法 将动物分为6组:正常对照组、模型组、假手术组、化淤通络胶囊大剂量组、化淤通络胶囊中剂量组、化淤通络胶囊小剂量组,中西医结合造模后,用药组给与化淤通络胶囊,再进行血液流变学检测.结果 ①化淤通络胶囊组时缺血性中风血液流变学确有显著调节作用;②化淤通络胶囊大、中、小剂量组对各指标影响无显著性差异,提示临床以小剂量为宜.结论 化淤通络胶囊治疗缺血性中风具有确切疗效.