三七中人参三醇甙对羊心浦氏纤维动作电位及延迟整流钾电流的影响

三七中人参三醇甙(PTS)2.5μg/ml及5.0μg/ml均能明显延长羊心浦氏纤维动作电位时程(APD)包括APD_(30),APD_(50),APD_(90),对动作电位幅度(APA)无明显影响。双微电极法电压钳实验证明,PTS能明显抑制羊心浦氏纤维延迟整流钾电流(I_x)的峰值,且此种抑制作用呈时间及剂量依赖性。揭示PTS通过阻滞延迟整流钾通道而延长APD。     

苄基四氢巴马汀细胞内用药对豚鼠乳头状肌动作电位和心室肌细胞延迟整流钾电流的作用

目的　研究将苄基四氢巴马汀(BTHP)导入细胞内对豚鼠乳头状肌动作电位及单个心室肌细胞延迟整流钾电流的影响。方法　利用外加电压脉冲将药物导入乳头状肌细胞内，并用标准微电极方法测定动作电位；利用浓度差扩散方式使药物进入单个心室肌细胞内，采用全细胞膜片钳技术记录延迟整流钾电流（I_K）。结果　100 μmol.L^-1 BTHP使APD₂₀和APD₉₀分别延长13.5%和20.5%。30 μmol.L^-1 BTHP使I_K和I_K,tail分别从（14.1±2.2) pA.pF^-1和(4.0±0.6) pA.pF^-1降至(9.4±1.3) pA.pF^-1和(2.1±1.0) pA.pF^-1，下降率分别为33.2%和35.3%。 该药使I_K和I_K,tail的I-V曲线幅度降低，对曲线形状影响不明显。结论　BTHP入细胞内后可阻滞延迟整流钾电流和延长动作电位时程。     

异紫堇啡碱对家兔窦房结及豚鼠心室肌动作电位的作用

用细胞内固定微电极技术观察了异紫堇啡碱(isocorydine)对家兔窦房结电活动、豚鼠心室肌动作电位及Ba²⁺诱发的豚鼠心室肌自发电活动的作用。结果表明,异紫堇啡碱能使窦房结细胞APA,SP₀,SP₄减小、APD₉₀延长、自律性降低。3 μM异紫堇啡碱能使心室肌细胞的APD₅₀,APD₉₀和ERP延长,300μM异紫堇啡碱则使心室肌细胞APD₅₀和APD₉₀缩短,但不缩短ERP,使ERP相对延长。300μM异紫茧啡碱亦能明显抑制Ba²⁺诱发的心室肌自发电活动。     

7-溴化乙氧苯四氢巴马汀抗心律失常作用的机理

7-溴化乙氧苯四氢巴马汀(7-bromoethoxybenzene-tetrahydropalmatine,EBP)10及30μmol/L均能明显延长豚鼠乳头状肌动作电位时程(APD),但对动作电位幅度(APA),静息电位(RP),超射(OS),零期最大上升速率(V_max)无显著影响。EBP能按剂量抑制犬浦氏纤维慢内向电流(I_si)及钾外向电流(I_x)的峰值。     

IHC-66对犬心室肌和浦顷野纤维的电生理作用

目的：观察IHC-66(3,6-dimethylamino-dibenzopyriodonium of ferric EDTA) 对离体犬心室肌与浦顷野纤维的电生理影响。 方法：采用心肌细胞内玻璃微电极技术。 结果：IHC-66可缩短犬心室肌动作电位复极20%和50%的时程,降低动作电位零相最大除极速率、缩短浦顷野纤维APD₅₀。 在较高浓度时, IHC-66还降低犬心室肌与浦顷野纤维动作电位振幅和延长动作电位APD₉₀。 结论：IHC-66对犬心室肌细胞APD₂₀和Vmax的抑制作用明显较浦顷野纤维强,对浦顷野纤维动作电位Vmax呈现频率依赖性抑制作用。     

肉毒碱对兔在体缺血心室肌细胞动作电位的影响

本实验观察了人工合成肉毒碱d,1-carnitine盐酸盐(VBt)对在位兔心急性心肌缺血早期左室肌细胞动作电位的影响。阻断冠脉引起动作电位振幅(APA)和零期最大除极速度(dv/dt)明显降低以及复极50%时程(APD₅₀)和复极90%时程(APD₉₀)明显缩短。VBt有延长心室肌细胞动作电位时程的作用(P<0.01),并能显著减轻缺血心肌细胞的APD₅₀和APD₉₀的缩短程度,但对APA和dv/dt的缺血性变化则无明显改善。     

牛磺酸镁配合物对获得性长QT综合征模型的抗心律失常作用研究

目的 研究牛磺酸镁配合物（TMCC）对获得性长QT综合征（LQTS）模型的抗心律失常作用及作用机制。方法 采用Langendorff逆行主动脉灌流酶解法,急性分离获得豚鼠单个心室肌细胞;建立表达KCNQ1/KCNE1基因的HEK293细胞模型。色原烷醇293B （5 μmol/L）用来建立LQTS模型,采用全细胞膜片钳技术记录TMCC （0.01、0.10、1.00 mmol/L）对正常和LQTS模型豚鼠心室肌细胞动作电位和缓慢激活延迟整流外向钾通道（I_Ks）电流的影响。结果 色原烷醇293B可以显著延长50%和90%复极化动作电位持续时间（APD₅₀和APD₉₀）,0.01、0.10、1.00 mmol/L TMCC可以显著减弱色原烷醇293B延长APD₅₀和APD₉₀的作用（P<0.05、0.01）。TMCC （0.01、0.10、1.00 mmol/L）对抗色原烷醇293B对I_Ks电流的抑制作用,减弱色原烷醇293B对I-V曲线的下移,0.1、1.0 mmol/L浓度组显著减弱色原烷醇293B对I_Ks电流的抑制作用（P<0.01）,呈现对抗LQTS的作用。结论 TMCC通过缩短动作电位复极时程,增大被抑制的I_Ks电流,发挥一定的抗LQTS的作用。     

硫酸锌对心肌慢反应电活动和哇巴因引起振荡后电位的影响

本文目的旨在观察硫酸锌对心肌慢反应电活动的影响,所得结果如下:(1) 0.1～0.3mmol硫酸锌能使高钾除极引起的豚鼠乳头肌慢反应动作电位APA和V_max降低,APD₅₀和APD₉₀)显著延长;(2) 0.1～0.3 mmol硫酸锌能抑制家兔离体窦房结细胞的自律性,使窦房结APA降低,APD₉₀延长,SP₀和SP₄减小;(3) 0.1 mmol硫酸锌可对抗0.4μmol哇巴因诱发的豚鼠心室肌振荡后电位,提高引起振荡后电位的哇巴因阈浓度。提示:锌抑制心肌慢反应电活动。     

抗心律失常药物作用的靶点——HERG K+通道

快速延迟整流钾电流(rapidly activating component of delayed rectifier potassium current，I_Kr)在心肌动作电位复极化过程中发挥重要作用。HERG基因编码心脏快速延迟整流钾通道的α亚基，HERG基因突变导致遗传性长QT间期综合征(long QT syndrome，LQTS)，另外I_Kr/HERG通道是绝大多数能引起心脏QT间期延长药物的作用靶标，其他一些化学结构不同的药物也可阻断该通道，引起QT间期延长，甚至发展成获得性心律失常。本文从门控机制及功能、HERG通道相关的心律失常、药物与通道相互作用机制、优化通道靶点的策略等四个方面综述I_Kr/HERG通道在抗心律失常方面的最新研究进展。     

他克林对培养大鼠海马神经元延迟整流钾电流和瞬间外向钾电流的影响

目的研究他克林对培养大鼠海马神经元上延迟整流钾电流(I_K)和瞬间外向钾电流(I_A)的影响。方法 大鼠海马神经元原代培养,全细胞膜片钳记录培养大鼠海马神经元上电压依赖性外向钾电流和瞬间外向钾电流变化。结果他克林明显抑制海马神经元延迟整流钾电流和瞬间外向钾电流,呈浓度依赖性,对延迟整流钾电流的敏感性高于瞬间外向钾电流。30 μmol·L^-1他克林显著影响I_K和I_A稳态激活曲线,使所有电流的V_1/2左移。结论他克林明显抑制延迟整流钾电流和瞬间外向钾电流,对延迟整流钾电流的敏感性高于瞬间外向钾电流。     

Acute alteration of cardiac ECG, action potential, I(Kr) and the human ether-a-go-go-related gene (hERG) K+ channel by PCB 126 and PCB 77

Polychlorinated biphenyls (PCBs) have been known as serious persistent organic pollutants (POPs), causing developmental delays and motor dysfunction. We have investigated the effects of two PCB congeners, 3,3′,4,4′-tetrachlorobiphenyl (PCB 77) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) on ECG, action potential, and the rapidly activating delayed rectifier K⁺ current (I_Kr) of guinea pigs' hearts, and hERG K⁺ current expressed in Xenopus oocytes. PCB 126 shortened the corrected QT interval (QTc) of ECG and decreased the action potential duration at 90% (APD₉₀), and 50% of repolarization (APD₅₀) (P < 0.05) without changing the action potential duration at 20% (APD₂₀). PCB 77 decreased APD₂₀ (P < 0.05) without affecting QTc, APD₉₀, and APD₅₀. The PCB 126 increased the I_Kr in guinea-pig ventricular myocytes held at 36 °C and hERG K⁺ current amplitude at the end of the voltage steps in voltage-dependent mode (P < 0.05); however, PCB 77 did not change the hERG K⁺ current amplitude. The PCB 77 increased the diastolic Ca²⁺ and decreased Ca²⁺ transient amplitude (P < 0.05), however PCB 126 did not change. The results suggest that PCB 126 shortened the QTc and decreased the APD₉₀ possibly by increasing I_Kr, while PCB 77 decreased the APD₂₀ possibly by other modulation related with intracellular Ca²⁺. The present data indicate that the environmental toxicants, PCBs, can acutely affect cardiac electrophysiology including ECG, action potential, intracellular Ca²⁺, and channel activity, resulting in toxic effects on the cardiac function in view of the possible accumulation of the PCBs in human body.     

A Carbohydrate Fraction, AIP1, from Artemisia Iwayomogi Reduces the Action Potential Duration by Activation of Rapidly Activating Delayed Rectifier K+ Channels in Rabbit Ventricular Myocytes

We investigated the effects of a hot-water extract of Artemisia iwayomogi, a plant belonging to family Compositae, on cardiac ventricular delayed rectifier K⁺ current (I_K) using the patch clamp technique. The carbohydrate fraction AIP1 dose-dependently increased the heart rate with an apparent EC₅₀ value of 56.1±5.5 µg/ml. Application of AIP1 reduced the action potential duration (APD) in concentration-dependent fashion by activating I_K without significantly altering the resting membrane potential (IC₅₀ value of APD₅₀: 54.80±2.24, IC₅₀ value of APD₉₀: 57.45±3.47 µg/ml). Based on the results, all experiments were performed with 50 µg/ml of AIP1. Pre-treatment with the rapidly activating delayed rectifier K⁺ current (I_Kr) inhibitor, E-4031 prolonged APD. However, additional application of AIP1 did not reduce APD. The inhibition of slowly activating delayed rectifier K⁺ current (I_Ks) by chromanol 293B did not change the effect of AIP1. AIP1 did not significantly affect coronary arterial tone or ion channels, even at the highest concentration of AIP1. In summary, AIP1 reduces APD by activating I_Kr but not I_Ks. These results suggest that the natural product AIP1 may provide an adjunctive therapy of long QT syndrome.     

2-[对-(二甲氨基)苯乙烯]氯化甲基吡啶对大鼠心电图、豚鼠左心房收缩及乳头肌动作电位的影响

2-[对-(二甲氨基)苯乙烯]氯化甲基吡啶(DSPM-Cl),是由氯取代2-[对-(二甲氨基)苯乙烯]碘化甲基吡啶(DSPM)上的碘而得。本文应用心电图、机械收缩描记方法及细胞内标准微电极技术,研究DSPM-Cl对大鼠心电图(ECG)、豚鼠心房肌量效曲线及对豚鼠乳头肌快反应动作电位(AP)、高钾除极慢反应动作电位(SAP)的影响。结果显示,DSPM-Cl(2mg·kg^-1)对大鼠有明显的负性频率、负性传导作用,分别使PP间期、PR间期延长达66.2%(P<0.01),17.0%(P<0.01),50μmol·L^-1能明显抑制左心房收缩力,非竟争性拮抗Iso及CaCl₂对豚鼠左心房的正性肌力作用,PD^2'分别为4.6,4.34,100μmol·L^-1DSPM-Cl延长动作电位时程APD₉₀,有效不应期(ERP),降低高钾除极豚鼠乳头肌0期最大上升速率Vmax,其作用与Ver相似,提示DSPM-Cl可能为钙拮抗剂。     

海兰地嗪对正常及肺动脉高压大鼠肺动脉平滑肌细胞延迟整流钾电流作用的比较

The delayed rectifier potassium currents of normal and chronic normobaric hypoxic pulmonary hypertensive rats and the effect of hernandezine on them were observed. The results showed that when cell membrane potential was held at -50 mV and command potential was larger than -50 mV, potential and time-dependent delayed rectifier potassium currents were recorded, and the delayed rectifier potassium current of pulmonary hypertensive rats was smaller than that of normal rats. When command potential was +70 mV, the effect of hernandezine (0.1 mmol·L^-1) on the increased delayed rectifier potassium currents of pulmonary hypertensive rats (31±13%) was smaller than that of normal rats (59±13%).     

青滕碱对豚鼠心肌动作电位和收缩力的影响

青藤碱2.7μmol/L以上,呈浓度依赖性地降低豚鼠乳头肌收缩力,延长动作电位时程和有效不应期。小剂量时,青藤碱能降低动作电位0相上升最大速率;较大剂量时,动作电位幅度也降低。用TTX处理豚鼠乳头肌所致的慢反应电位,青藤碱能够抑制。此外,青藤碱能对抗乙酰胆碱缩短豚鼠左房肌动作电位时程的作用。结果提示:青藤碱对Na⁺,Ca²⁺和K⁺的跨膜转运均有抑制作用。     

Electrophysiological effects of EGIS-7229, a new antiarrhythmic agent, in isolated mammalian and human cardiac tissues

The cellular electrophysiological effects of EGIS-7229 (5-chlor-4-[N-(3,4-dimethoxy-phenyl-ethyl)-amino-propylamino]-3(2H)-pyridazinone fumarate), a novel antiarrhythmic agent, was studied using conventional microelectrode techniques in canine cardiac Purkinje fibers and papillary muscle preparations obtained from man, rabbits and guinea pigs. Low concentration of EGIS-7229 (3 μmol/l) selectively lengthened action potential duration (both APD₅₀ and APD₉₀) in all preparations. The effect of higher concentrations (30–100 μmol/l) of EGIS-7229 on action potential duration was variable depending on the preparation studied: in rabbit and human papillary muscles both APD₅₀ and APD₉₀ were lengthened, in canine Purkinje fibers APD₉₀ was lengthened but APD₅₀ was shortened, while in guinea pig papillary muscles both APD₅₀ and APD₉₀ were shortened by high concentrations of the drug. At these higher concentrations EGIS-7229 also decreased the maximum velocity of action potential upstroke (V _max) and depressed the plateau of action potentials without affecting the resting membrane potential or action potential amplitude. Both reduction of V _max and lengthening of APD were frequency dependent. The former effect was more prominent at higher pacing frequencies, while the latter was more pronounced at lower driving rates. In guinea pig papillary muscle, the time constant of recovery from V _max-block was 719 ± 33 ms (n = 18) and the rate of onset of the block was 1.81 ± 0.06 AP^–1 (n = 16) in the presence of 100 μmol/l EGIS-7229. EGIS-7229 had a complex action on refractoriness in guinea pig papillary muscles: ERP was lengthened at low concentrations (3 to 10 μmol/l), unchanged at 30 μmol/l and shortened at 100 μmol/l. The ratio of ERP/APD₉₀, however, was significantly increased at concentrations higher than 3 μmol/l. In canine Purkinje fiber, when the delayed rectifier K current (I_K) was blocked by d-sotalol (60 μmol/l) and APD was shortened back to its control value by additional application of nicorandil (15 μmol/l), APD was not affected by 3 μmol/l but was shortened by 30 μmol/l of EGIS-7229. 100 μmol/l EGIS-7229 shortened APD in guinea pig papillary muscle. This effect of EGIS-7229 was effectively prevented by nifedipine pretreatment (10 μmol/l). In this preparation, EGIS-7229 also decreased the V _max of the slow action potential, evoked in the presence of 20 mmol/l external K⁺ plus 0.5 mmol/l Ba²⁺. It is likely that EGIS-7229 at low concentrations blocks I_K in human, canine, rabbit and guinea pig cardiac preparations, but at higher concentrations also inhibits Ca and Na currents. Therefore, EGIS-7229 appears to carry mixed class III, IV and IB antiarrhythmic properties. Received: 8 July 1996 / Accepted: 23 October 1996     

Efects of benzyltetrahydropalmatine ?

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关附甲素对豚鼠心室肌细胞延迟整流钾电流的抑制作用

用全细胞膜片钳制技术研究关附甲素对豚鼠心室肌细胞延迟整流钾电流的作用。结果表明,关附甲素100μmol·L^-1对延迟整流钾电流有明显的抑制作用。去极化2200和3850ms时,I_k分别由293±90和290±90pA减小至227±59和231±66pA,这种抑制作用与去极化持续时间无关。关附甲素对内向整流钾电流无影响。提示关附甲素延长心肌复极化时间似与抑制延迟整流钾电流的作用有关。