胺碘酮对大鼠肥厚心肌细胞急性电生理作用的研究

目的研究胺碘酮对正常心肌与肥厚心肌细胞急性电生理作用的区别,探讨胺碘酮在病态心肌应用中的合理性。方法SPRAGUEDAWLAY(SD)大鼠缩窄腹主动脉,建立左心室肥厚模型。应用膜片钳技术,选用不同浓度胺碘酮灌流正常心肌细胞和肥厚心肌细胞,观察内向电流:钠流(INA)、L型钙流(ICAL)和外向电流:延迟整流性钾流(IK)、瞬间复极钾流(ITO)、内向整流性钾流(IK1)。以多非利特(DOFETILIDE)阻滞延迟整流性钾流的快速成分(IKR),所测IK代表延迟整流性钾流的缓慢成分(IKS)。结果(1)肥厚心肌细胞电重构特征为肥厚心肌INA、ICAL与正常心肌相近,但肥厚心肌的外向电流较正常心肌减小,表现在IK、IKS、ITO和IK1的电流密度降低。(2)胺碘酮50ΜMOL/L抑制正常心肌细胞(59.0±4.4)%的ICAL,对肥厚心肌ICAL的抑制不明显,仅抑制(16.7±8.0)%的ICAL;胺碘酮抑制正常心肌细胞和肥厚心肌细胞INA的半抑制浓度(IC50)分别为9.2ΜMOL/L和5.9ΜMOL/L;胺碘酮50ΜMOL/L阻滞正常心肌细胞和阻滞肥厚心肌细胞ITO分别为(55.9±5.5)%和(23.0±2.8)%;胺碘酮对正常心肌细胞或肥厚心肌细胞IK1的影响较小;胺碘酮对IKS阻滞程度,肥厚心肌大于正常心肌,胺碘酮10ΜMOL/L抑制正常心肌和肥厚心肌IKS分别为(21.6±5.6)%和(42.7±9.2)%。提示胺碘酮阻滞肥厚心肌细胞INA、IKS的敏感性大于正常心肌细胞,阻滞ICAL、ITO、IK1的敏感性又低于正常心肌细胞。结论胺碘酮对电重构的肥厚心肌细胞急性电生理反应,有利于其在抗心律失常中的应用。     

胺碘酮对肥厚心肌钙调蛋白激酶活性的影响

目的观察口服胺碘酮对肥厚心肌细胞钙调蛋白激酶(CaMK)活性的影响,探讨胺碘酮抗心律失常的作用机制。方法30只家兔随机分为假手术组、心肌肥厚组和胺碘酮组,每组10只,喂养3个月,制备兔左室楔形心肌块。同步记录楔形心肌块容积心电图和内、外膜心肌细胞跨膜动作电位(TAP),程序电刺激诱发室性心律失常,并观察各组QT间期、跨室壁复极离散度(TDR)、早期后除极(EAD)和尖端扭转型室性心动过速(Tdp)的诱发率。利用放射免疫法测定心肌细胞CaMK活性。结果胺碘酮组和心肌肥厚组QT间期、内外膜心肌细胞TAP复极90%时程(APD90)和TDR均较假手术组明显延长(P<0.01),胺碘酮组QT间期和内、外膜心肌细胞APD90与心肌肥厚组相比进一步延长(P<0.05),但对TDR无明显影响。与假手术组比较,心肌肥厚组EAD和Tdp的发生率较假手术组明显升高(P<0.01),胺碘酮组EAD和Tdp的发生率较心肌肥厚组降低(P<0.05)。心肌肥厚组心肌细胞CaMK活性较假手术组明显升高,胺碘酮组CaMK活性较心肌肥厚组降低(P均<0.05)。结论胺碘酮抗心律失常的作用机制可能部分与抑制CaMK活性有关。     

胺碘酮对心肌梗死一月后非梗死区心室肌细胞快钠通道电流跨壁异质性的影响

探讨胺碘酮对心肌梗死 (MI)后非梗死区心肌细胞快钠通道电流 (INa)跨壁异质性的影响。 36只兔随机分为4组 ,其中两组建立急性MI动物模型 ,分别为胺碘酮组和MI组 ,其余两组为正常对照组和假手术对照组。 1个月后 ,用膜片钳技术研究左室非梗死区三层心肌细胞INa的改变。结果 :正常对照组左室三层细胞的钠电流存在异质性 ,M细胞的峰值INa是心内膜 (Endo)和心外膜层 (Epi)的 2倍多 ;M细胞的INa失活最快 ;对照组与假手术组无明显差别。MI组三层细胞的INa电流密度下降 ,以M细胞变化最显著 ,INa稳态失活曲线均左移 ,以Epi变化最显著 ;胺碘酮组三层细胞INa电流密度下降显著 ,稳态失活曲线左移最明显并趋向一致 ,灭活后恢复曲线均恢复减慢。结论 :左室心肌细胞的INa存在跨壁异质性 ;MI对INa的跨壁异质性有明显影响 ;而胺碘酮减弱MI后INa的跨壁异质性。     

胺碘酮和索他洛尔对家兔不同部位心室肌细胞电生理特性的影响

目的　观察胺碘酮和索他洛尔对家兔跨左心室壁不同部位心肌细胞电生理特性的影响 ,从组织水平探讨两种药物致尖端扭转性室性心动过速 (torsadedepointes,TdP)发生率不同的原因。方法　采用标准玻璃微电极记录技术 ,记录心外膜心肌、中层心肌和心内膜心肌的跨膜动作电位 (trans membranceactionpotential,TAP)。在不同基础周长 (basiccyclelength ,BCL)刺激下 (2 50～ 2 0 0 0ms) ,分别观察 0 3～ 3 0 μmol·L- 1 浓度的胺碘酮和 1 0～ 1 0 0 μmol·L- 1 浓度的索他洛尔对 3种心肌TAP的影响。结果　胺碘酮频率依赖性和浓度依赖性地延长 3种心肌的动作电位时限 (actionpotentialduration ,APD90 ) ,由于 3种心肌的APD90 延长程度近似 ,用药后跨心室壁复极离散度 (transmuraldispersionofre polarization ,TDR)无明显增加。索他洛尔呈逆频率依赖性和浓度依赖性地延长 3种心肌的APD90 ,与心外膜心肌和心内膜心肌相比 ,中层心肌的APD90 延长更明显 ,使TDR明显增加 ,且随着剂量的增加这种作用更为显著。在 2 0 0 0msBCL刺激时 ,1 0 0 μmol·L- 1 浓度的索他洛尔诱发早期后除极 (earlyafterde polarization ,EAD) ,胺碘酮无此作用。 结论　胺碘酮和索他洛尔对跨心室壁不同部位心肌细胞电生理特性产生不同的     

葛根素对大鼠心肌细胞Ito、ICa-L、INa离子通道的影响

目的通过研究葛根素对大鼠心肌细胞离子通道瞬时外向钾电流（Ito）、L-型钙电流（ICa-L）、钠电流（INa）的影响,探讨葛根素抗心律失常的机制。方法采用Langendoff胶原酶灌注加浸泡法分离大鼠心室肌细胞,分别用膜片钳全细胞记录各组Ito、ICa-L、INa。结果1.29.6 mmol/L葛根素对Ito通道没有明显的抑制效应,在高浓度（19.2mmol/L）时,葛根素可抑制Ito电流,达到正常对照组的（21±6）%（n=5,P<0.05）。低浓度E-4031对Ito通道没有抑制效应,但高浓度（19.2 mmol/L）E-4031可抑制Ito电流的（19±4）%（n=5,P<0.05）;葛根素（1.219.2mmol/L）和E-4031（1.219.2 mmol/L）对ICa-L和INa无明显的抑制作用。结论大剂量葛根素对大鼠心肌细胞Ito有抑制作用。     

胺碘酮对犬正常心肌与肥厚心肌跨室壁不应期离散的影响

目的探讨胺碘酮对正常心肌与肥厚心肌跨室壁不应期离散(TDR)的影响。方法采用特制电极直接测量在体三层心肌的有效不应期(ERP)的方法,观察胺碘酮对犬正常心肌和肥厚心肌三层心肌ERP和TDR的影响。结果犬正常心肌在用胺碘酮前后三层之间的ERP无显著差异。犬肥厚心肌各层的ERP之间有显著性差异,应用胺碘酮后TDR明显缩小。正常心肌各层的TDR在循环长度改变时其数值差异无显著性,而在肥厚心肌TDR的差异显著。结论犬肥厚心肌的三层心肌间存在显著的TDR。胺碘酮可使肥厚心肌三层心肌的TDR减小。长-短间期或短-长间期刺激可使肥厚心肌的TDR增大,应用胺碘酮后,TDR无显著差异。     

阿魏酸钠与胺碘酮对家兔心室肌细胞L型钙通道电流的影响

目的探讨阿魏酸钠对家兔心室肌细胞膜L型钙通道电流(ICa-L)的影响。方法酶解法急性分离兔单个心室肌细胞,以经典的Ⅲ类抗心律失常药物胺碘酮为对照,应用膜片钳全细胞记录技术观察3,10,30,100μmol/L的阿魏酸钠对心室肌细胞膜ICa-L的作用。结果阿魏酸钠及胺碘酮均呈浓度依赖性抑制L型钙电流。3,10,30,100μmol/L的阿魏酸钠对ICa-L的抑制率分别为11.1%±2.4%,26.9%±6.2%,40.5%±5.0%,61.9%±5.5%(P<0.05);1,3,10,30μmol/L的胺碘酮对ICa-L的抑制率分别为21.1%±3.8%,32.6%±2.6%,52.6%±4.6%,71.4%±7%(P<0.05);半数抑制浓度分别为32.6及9.5μmol/L,阿魏酸钠的抑制作用弱于胺碘酮(P<0.05)。阿魏酸钠及胺碘酮均能使ICa-L电流-电压曲线上移,稳态激活曲线右移,失活曲线左移,并可减慢钙通道灭活后的恢复过程。结论阿魏酸钠对ICa-L具有浓度依赖性阻滞作用,使ICa-L的激活减慢,失活加快,并且失活后的恢复时间延长,可能是其抗心律失常作用的电生理机制之一。     

兔界嵴细胞离子通道特性研究

目的研究生理状态下及异丙肾上腺素灌流对兔界嵴(CT)与梳状肌(PM)细胞动作电位(AP)及钠电流(INa)、短暂外向钾电流(Ito)、L型钙电流(ICa-L)、延迟整流钾电流(IK)及内向整流性钾电流(IK1)的影响,探讨CT与房性心律失常的关系。方法酶解法分离兔CT及PM细胞,利用全细胞膜片钳技术,记录生理状态下及异丙肾上腺素灌流后CT与PM细胞AP及INa、Ito、ICa-L、IK及IK1的变化。结果①生理状态下,CT细胞动作电位时程(APD)较长,可见明显的平台期;PM细胞AP形态与普通心房肌细胞相似,1期复极迅速,平台期短,类似三角形。②生理状态下,CT细胞Ito电流密度比PM细胞明显降低(7.13±0.38 pA/pF vs 10.70±0.62 pA/pF,n=9,P<0.01),而INa、Ito、ICa-L、IK及IK1则无明显差别。③异丙肾上腺素灌流时CT与PM细胞APD20、APD50、APD90均延长(n=8,P<0.01);指令电位+50 mV时,CT与PM细胞Ito电流密度均减少(n=9,P<0.01)而IK均增加(n=8,P<0.05);指令电位+10 mV时,CT与PM细胞ICa-L电流密度均增加(n=9,P<0.01);IK1在两种心肌细胞均无明显差异。结论 CT与PM细胞AP差异与Ito有关。异丙肾上腺素灌流时ICa-L与IK增强,Ito抑制使CT与PM细胞APD延长,触发机制可能是CT参与房性心律失常的机制之一。     

阿魏酸钠对家兔心室肌细胞钾通道电流的影响

目的:探讨阿魏酸钠对家兔心室肌细胞膜延迟整流钾电流快速与缓慢激活成分(IKr、IKs)、内向整流钾电流(IK1)、瞬时外向钾电流(Ito)的影响.方法:酶解法分离单个家兔心室肌细胞,以经典的Ⅲ类药胺碘酮为对照,采用全细胞膜片钳技术记录浓度为3.0、10.0、30.0,100.0 μmol/L的阿魏酸钠对IKr,IKs、IK1、Ito的作用.结果:阿魏酸钠的作用弱于胺碘酮,二者均可浓度依赖性抑制IKr、ILs时间依赖性外向电流及尾电流(IKr,tail、IKs,tail).不同浓度的阿魏酸钠对IKr,tail的抑制率为:(12.1±2.5)%、(24.1±3.0)%、(47.0±5.8)%及(58.5±8.3)%(n=5,P＜0.05);对IKs,tail的抑制率为:(15.6±6.4)%、(27.1±6.5)%、(45.6±5.8)%及(51.8±6.6)%(n=5,P＜0.05),其对IKr,tail及IKs,tail的半数抑制浓度(IC50)均大于胺碘酮(43.6:3.48 μmol/L,44.9:5.11 μmol/L).30.0、100.0 μmol/L阿魏酸钠及10.0、30.0 μmol/L胺碘酮可使IK1的I-V曲线左移,在-100 mV及-20 mV测试电压下,阿魏酸钠对IK1内向、外向电流抑制率小于胺碘酮(n=5,P＜0.05).阿魏酸钠与胺碘酮均不影响Ito及其I-V曲线.结论:阿魏酸钠复合阻滞复极期多种钾电流,可能是其抗心律失常作用的电生理机制之一.     

心脏移植病人的心肌胺碘酮和去乙基胺碘酮浓度

测定药物及其代谢产物的心肌浓度将增进对该药作用机制及电生理作用的了解。以前有过二篇报道记述了右心房活检标本的胺碘酮浓度。本文报告从四个心腔取得心肌标本,测定胺碘酮及去乙基胺碘酮的浓度。许多心脏活性药物的心肌浓度明显高于     

Ion channels and arrhythmias

Changes in ionic currents through ion channels of the myocardial cell membrane have to be regarded as main cause of cardiac arrhythmias. Three basic arrhythmogenic mechanisms are responsible for the initiation of tachyarrhythmias: 1. The disturbance of normal automaticity in cardiac pacemaker cells dependent on the currents If, ICa-L, ICa-T or IK-ACh,Ado and the occurrence of abnormal automaticity in atrial and ventricular working myocardium based on the currents ICa-L, INa, IK, IK1 or IK-ACh,Ado. 2. Triggered activity which may be recognized by the appearance of early (EAD) or late afterdepolarizations (LAD). EAD are mainly due to inhibition of the outward currents IKr and IKs and are favoured by an increase in the inward currents INa and ICa-L, respectively. Typical arrhythmias are torsade de pointes occurring during treatment with K(+)-channel inhibitors (e.g. sotalol) or in patients with QT-syndrome. LAD may be observed during Ca(2+)-overload of the myocardial cell (digitalis intoxication, catecholamines) and are based on the transient inward current Iti, which is build up by the participation of the currents INa/Ca, INS and ICa-L. 3. Reentry mechanisms are the most frequent cause of tachyarrhythmias. They originate in an anatomically defined excitation circle with unidirectional block. Na(+)- and Ca(2+)-channel dependent disturbances of conduction with long excitable gap may be distinguished from Na(+)-channel dependent disturbances of conduction and refractory period with short excitable gap. Interruption of reentry is possible in the first case by depression of conduction and excitability (Na(+)- or Ca(2+)-channel blockers), in the second case by increase in refractory period (K(+)- or Na(+)-channel blockers).     

芍药苷对心脏钾通道电生理功能的影响

目的研究芍药苷对内向整流钾电流(IK1)、瞬时外向钾电流(Ito)以及延迟整流钾电流(IKs和IKr)的作用。方法用全细胞膜片钳技术记录大鼠心室肌细胞的Ito和IK1电流。而IKs和IKr电流在转染相应质粒的HEK293细胞上记录。对比芍药苷使用前后的电流图,观察芍药苷对各种离子通道电流的影响。结果在-100mV测试电压下,100μmol/L的芍药苷能使IK1峰值密度从(-25.26±8.21)pA/pF降至(-17.65±6.52)pA/pF,平均抑制率为30.13%(n=6,P<0.05),但对其反转电位以及内向整流特性无影响。此外,100μmol/L芍药苷对Ito、IKs和IKr电流无明显作用。结论芍药苷对IK1电流具有明显的抑制作用,而对Ito、IKs及IKr无明显作用。     

稳心颗粒甘松提取物对大鼠心室肌细胞钠电流和瞬时外向钾电流激活动力学的影响

目的研究步长稳心颗粒中甘松提取物对大鼠心室肌细胞钠电流(INa)、瞬时外向钾电流(Ito)激活动力学的影响。方法采用全细胞膜片钳技术,研究10 g/L甘松提取物对急性分离的成年大鼠心室肌细胞INa、Ito激活动力学的影响。结果①10 g/L甘松提取物使大鼠心室肌细胞INa峰值(INa,max)从-58.96±2.71 pA/pF降至-31.66±1.29 pA/pF(n=5,P<0.01);②10 g/L甘松提取物使Ito峰值(Ito,max)由3.40±1.52 pA/pF降到1.43±0.64 pA/pF(n=7,P<0.05)。10 g/L甘松提取物对INa和Ito的抑制率分别达38.2%和57.9%。结论10 g/L甘松提取物对大鼠心室肌细胞INa、Ito具有显著抑制作用。     

二十二碳六烯酸对大鼠心室肌细胞钠通道和瞬时外向钾通道的影响

目的 研究二十二碳六烯酸(DHA)对大鼠心室肌细胞钠通道电流(INa)和瞬时外向钾通道电流(Ito)的动力学影响.探讨DHA抗心律失常的机制.方法 采用膜片钳技术在全细胞模式下,记录20、40、60、80、100和120μmol/L DHA对大鼠心室肌细胞INa和Ito的影响.结果 (1)DHA对INa呈浓度依赖性阻滞,使稳态失活曲线左移、失活后恢复时间延长,对稳态激活曲线无影响.在指令电压-30 mV,上述浓度DHA对INa阻滞分别为(1.51±1.32)%、(21.13±4.62)%、(51.61±5.73)%、(67.62±6.52)%、(73.49±7.59)%和(79.95±7.62)%(P<0.05,n=20),DHA对INa的半效作用浓度为(47.91±1.57)μmol/L.(2)DHA对Ito呈浓度依赖性阻滞,使稳态失活曲线左移、失活后恢复时间延长,对稳态激活曲线无影响.在指令电压+70 mV,上述浓度DHA对Ito阻滞分别为(2.61 ±0.26)%、(21.79±4.85)%、(63.11±6.57)%、(75.52 ±7.26)%、(81.82 ±7.63)%和(84.33±8.25)%(P<0.05,n=20),DHA对Ito的半效作用浓度为(49.11±2.68)μmol/L.结论 DHA对钠通道和瞬时外向钾通道的抑制作用可能是其抗心律失常机制之一.

Abstract：

Objective To investigate the effects of docosahexaenoic acid(DHA)on sodium channel current(INa)and transient outward potassium channel current(Ito)in rat ventricular myocytes and to evaluate potential anti-arrhythmic mechanisms of DHA.Methods INa and Ito of individual ventricular myocytes were recorded by patch-clamp technique in whole-cell configuration at room temperature.Effects of DHA at various concentrations(0,20,40,60,80,100 and 120 μmol/L)on INa and Ito were observed.Results (1) INa was blocked in a concentration-dependent manner by DHA,stably inactivated curves were shifted to the left,and recover time from inactivation was prolonged while stably activated curves were not affected by DHA.At-30 mV,INa was blocked to(1.51 ±1.32)%,(21.13±4.62)%,(51.61 ±5.73)%,(67.62 ±6.52)%,(73.49±7.59)%and(79.95±7.62)%in the presence of above DHA concentrations(all P<0.05,n=20),and half-effect concentration(EC50)of DHA on INa was(47.91±1.57)μmol/L(2) Ito were also blocked in a concentration-dependent manner by DHA,stably inactivated curves were shifted to the left,and recover time from inactivation was prolonged with increasing concentrations of DHA,and stably activated curves were not affected by DHA.At+70 mV,Ito was blocked to(2.61 ±0.26)%,(21.79±4.85)%,(63.11 ±6.57)%,(75.52 ±7.26)%,(81.82 ±7.63)%and(84.33±8.25)%,respectively,in the presence of above DHA concentrations(all P<0.05,n=20),and the EC50 of DHA on Ito was(49.11±2.68)μmol/1.Conclusion The blocking effects of DHA on APD and Ito may serve as one of the anti-arrhythmia mechanisms of DHA.     

Effects of gender difference on cardiac myocyte dysfunction in streptozotocin-induced diabetic rats

The main characteristics of type 1 diabetic cardiomyopathy include depressed contractility and altered electrophysiological properties in ventricular myocytes. The goal of the present study was to determine the potential influence of gender in the diabetes-induced pathogenesis of ventricular myocyte function. Diabetes in both male and female rats was induced by a single intravenous injection of streptozotocin (STZ). Diabetic rats exhibited hyperglycemia and reduced body weight gain in both male and female groups. Neither contractile profiles nor activity of three types of K+ channels of ventricular myocytes was significantly different between nondiabetic male and female rats. Ventricular myocytes isolated from diabetic rats exhibited significant depression in cell contraction and relaxation, which was associated with depression of intracellular Ca2+ ([Ca2+]i) transient. The degrees of contractile depression were comparable in ventricular myocytes obtained from both male and female diabetic rats. Similarly, diabetes depressed three types of outward K+ currents (Ito, Ik, and Iss) to the same extent in both gender myocytes. These data demonstrate that in this animal model of diabetes, gender difference in cardiac myocyte functions was eliminated.     

Ionic mechanisms of electrical remodeling in human atrial fibrillation

OBJECTIVES: Atrial fibrillation (AF) is associated with a decrease in atrial ERP and ERP adaptation to rate as well as changes in atrial conduction velocity. The cellular changes in repolarization and the underlying ionic mechanisms in human AF are only poorly understood. METHODS: Action potentials (AP) and ionic currents were studied with the patch clamp technique in single atrial myocytes from patients in chronic AF and compared to those from patients in stable sinus rhythm (SR). RESULTS: The presence of AF was associated with a marked shortening of the AP duration and a decreased rate response of atrial repolarization. L-type calcium current (ICa,L) and the transient outward current (Ito) were both reduced about 70% in AF, whereas an increased steady-state outward current was detectable at test potentials between -30 and 0 mV. The inward rectifier potassium current (IKI) and the acetylcholine-activated potassium current (IKACh) were increased in AF at hyperpolarizing potentials. Voltage-dependent inactivation of the fast sodium current (INa) was shifted to more positive voltages in AF. CONCLUSIONS: AF in humans leads to important changes in atrial potassium and calcium currents that likely contribute to the decrease in APD and APD rate adaptation. These changes contribute to electrical remodeling in AF and are therefore important factors for the perpetuation of the arrhythmia.     

依那普利和厄贝沙坦及血管紧张素-(1-7)对快速心房起搏犬心房肌瞬时外向钾电流及L型钙电流的影响

目的研究依那普利、厄贝沙坦及血管紧张素-(1-7)[Ang-(1-7)]对快速心房起搏犬心房肌瞬时外向钾电流(Ito)、L型钙电流(ICa-L)及其基因表达的影响。方法普通杂种犬30只,分为假手术(S)组、心房起搏对照(C)组、依那普利(EN)组、厄贝沙坦(IB)组及Ang-(1-7)(A)组,每组6只。C组以特制起搏器维持500次/分右房起搏2周,S组安置起搏器但不予起搏刺激。EN组、IB组和A组,右房起搏同时分别给予依那普利、厄贝沙坦、Ang-(1-7)治疗至实验结束。观察心房肌细胞Ito、ICa-L和动作电位时程(APD)的变化,以及ItoKv4.3亚单位和ICa-Lα1C亚单位mRNA在心房组织的表达。结果与S组比较,心房起搏后,各刺激频率下C组和EN组APD复极达90%时程(APD90)显著缩短。IB组和A组,APD90缩短不显著。S组、IB组、A组,随着刺激频率增加APD90缩短,C组、EN组无此特征。除EN组外,不同刺激频率下,各组复极达50%时程(APD50)变化均不显著。与S组比较,C组、IB组Ito最大电流密度显著降低(P0.05),EN组显著升高(P0.01);C组、EN组、IB组ICa-L最大电流密度低于S组(P0.01)。C组、IB组Kv4.3mRNA转录水平低于S组(P0.01),EN组显著升高(P0.01)。C组、EN组、IB组、A组ICa-Lα1CmRNA转录水平较S组显著降低(P0.01)。结论依那普利、厄贝沙坦和Ang-(1-7)对快速心房起搏犬心房肌Ito、ICa-L及APD的影响不同。     

丹酚酸B对大鼠心室肌细胞瞬时外向钾电流和L型钙电流的阻滞作用

目的研究从丹参中分离提取的药物单体——丹酚酸B对大鼠心肌细胞上的瞬时外向钾电流(Ito)、内向整流钾电流(IK1)和L型钙电流(ICa,L)的电生理学作用。方法用酶解法分离大鼠心室肌细胞,全细胞膜片钳技术记录Ito、IK1和ICa,L。每个细胞采用加药前后自身对照,用含100μmol/L丹酚酸B的细胞外液灌流心室肌细胞,记录加药前、后的电流,所有数据均在细胞破膜后20min内完成。结果 100μmol/L的丹酚酸B对Ito和ICa,L具有抑制作用,使Ito和ICa,L最大激活峰值电流密度下降,电流密度-电压曲线下移;且丹酚酸B主要抑制Ito的快速电流成分Itof,而对Ito的缓慢电流成分Itos无明显作用。在60mV测试电压下,Itof的最大激活峰值电流密度从23.51±3.29pA/pF降为16.85±2.36pA/pF,抑制率为28.31%±10.6%(n=8,P0.05)。在-10mV测试电压下,100μmol/L丹酚酸B作用后ICa,L的最大激活峰值电流密度从-8.66±-2.40pA/pF降为-5.91±-2.14pA/pF,抑制率为31.84%±10.23%(n=11,P0.05)。丹酚酸B使Ito通道失活后的恢复减慢,但不改变ICa,L的通道动力学。丹酚酸B对IK1无显著作用。结论丹酚酸B对Ito和ICa,L具有阻滞作用,而对IK1无显著作用。