苄基四氢巴马汀对豚鼠心室肌细胞快激活延迟整流钾电流的作用

目的研究苄基四氢巴马汀(BTHP)对心室肌细胞快激活(I_kr)延迟整流钾电流的作用。方法 用全细胞膜片钳技术记录豚鼠心室肌细胞钾离子通道电流。结果BTHP在1～100 μmol·L^-1以浓度依赖性方式阻滞I_kr,其IC₅₀为13.5 μmol·L^-1(95%可信范围:11.2～15.8 μmol·L^-1)。30 μmol·L^-1 BTHP可使I_kr及I_kr,tail分别降低(31±4)%和(36±5)% (N=6,P<0.01)。与多数III类抗心律失常药物不同,BTHP可频率依赖性地抑制I_kr。该药主要改变I_kr的失活过程,可使I_kr的失活时间常数(τ)从(238±16) ms降至(196±14) ms,而对I_kr的激活动力学影响不大。结论BTHP对I_kr有明显的抑制作用,且其阻滞作用呈现频率依赖性特征。     

氟卡尼电压和频率依赖性抑制豚鼠心房细胞迟发性外向钾电流(英文)

本文用单细胞钳法研究了氟卡尼(flecainide,F1e)对豚鼠心房单细胞膜电流的影响,发现Fle频率依鞍性延长动作电位时程,并且浓度和频率依赖性减低迟发性外向钾电流和尾电流,Fle对保持电流作用不显著,Fle抗房性心律失常机制是电压依赖性抑制外向钾电流,Fle显著影响复极过程,故不符合I_c类抗心律失常药物。     

苄基四氢帕马丁对豚鼠心房单细胞延迟外向钾电流的电压依赖性抑制作用

本文采用膜片钳封接技术，在豚鼠心房单细胞研究了苄基四氢帕马丁对动作电位和跨膜离子流的作用。结果发现，该药可显著地延长心房细胞的动作电位时程，并具有频率一浓度依赖性，但是，对动作电位时程复极到２０％时的值影响不明显，而且亦呈频率一浓度依赖性特异地抑制延迟外向钾电流和外向尾电流。去极化至－２０ｍＶ到＋６０ｍＶ间，这种抑制作用较强。不过药物对保持电流无明显影响。提示，该药抗心律失常和延长动作电位作用的主要机制是抑制延迟外向钾电流和尾电流。     

苄基四氢巴马汀对表达于非洲爪蟾卵母细胞及中华大蟾蜍卵母细胞的延迟整流钾电流的抑制作用

苄基四氢巴马汀对表达于非洲爪蟾卵母细胞及中华大蟾蜍卵母细胞的延迟整流钾电流的抑制作用童秋生，夏国瑾，姚伟星，江明性，白小川，包永德（同济医科大学基础医学院药理学教研室，武汉４３００３０；中国科学院上海生理学研究所，上海２０００３１）苄基四氢巴马汀（ｂ...     

Study on bradycardia induced by diltiazem in the rabbit sinoatrial node

Effects of 3-(acetyloxy)-5-[2-(dimethylamino)ethyl]-2, 3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one (diltiazem) on the membrane currents of rabbit sinoatrial node cells were examined using the double microelectrode voltage clamp technique. The transmembrane slow inward current (Isi) was reduced after 0.5 mumol/l diltiazem perfusion and Isi was nearly completely suppressed by 2.2 mumol/l diltiazem. As to the blockade of Isi, diltiazem revealed a dose-dependent fashion. Diltiazem also produced a slight decrease of both the steady-state current during depolarization and the tail current after repolarization in these concentration ranges, while the hyperpolarization activated current (Ih) was not affected significantly. Furthermore, higher concentration of diltiazem (10 mumol/l) decreased the steady-state outward current amplitude during depolarization, implying that diltiazem might reduce the potassium outward current (Ik). It is concluded that diltiazem suppressed Isi in a use-dependent manner, not surprisingly, but the drug exerted an additional effect of a decrease in Ik of sinoatrial node cells.     

Inhibition of myocardial K+ channels by bromobenzoyl-methyladamantylamine, an adamantane derivative

The effect of bromobenzoyl-methyladamantylamine (BMA) on transmembrane potentials and contractility of atrial and ventricular myocardium of guinea-pig and cat, as well as on transmembrane ionic currents of the frog atrial trabeculae was studied using conventional glass microelectrode and double sucrose-gap voltage clamp techniques. BMA markedly prolonged the action potential duration, depolarized the cell membrane, reduced the rate of rise of the action potential and exerted a positive inotropic effect on non-clamped myocardial preparations. The drug-induced pacemaker activity in ventricular working muscle of cat. Moreover, BMA antagonized the effects of the K+ channel activator acetylcholine in a dose-dependent manner. BMA was found to induce slow response action potentials in K+ -depolarized ventricular myocardium of guinea-pig. In voltage clamp experiments, BMA reduced the outward K+ current but had no effect on either rapid inward Na+ or slow inward Ca2+ currents. The results suggest that BMA is capable of selectively blocking the myocardial K+ channels.     

苄基四氢巴马汀对豚鼠心室肌细胞慢激活延迟整流钾电流及其尾电流的作用(英文)

目的　研究苄基四氢巴马汀 (BTHP)的抗心律失常机理。方法　采用全细胞膜片钳技术记录心室肌细胞慢激活延迟整流钾电流 (IKs)及其尾电流(IKs ,tail)。结果　BTHP在 1～ 10 0 μmol·L- 1的范围内以浓度依赖性、电压依赖性和频率依赖性方式阻滞IKs ,tail,其IC50 为 9.3μmol·L- 1(95 %可信限 :7.8～11.8μmol·L- 1)。BTHP 30 μmol·L- 1可使IKs 及IKs,tail分别降低 (40± 6 ) %和 (39± 5 ) % (P <0 .0 1)。BTHP可以抑制IKs ,tail。该药主要使IKs ,tail的失活时间常数缩短 ,从而使IKs ,tail 失活速度增加 ,而对IKs,tail的激活动力学影响不大。结论　BTHP对IKs有明显的抑制作用。     

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。     

苄基四氢巴马汀对豚鼠和大鼠心室肌细胞钾电流的作用

目的:研究苄基四氢巴马汀(BTHP)对心室肌细胞快激活(I_(Kr))和慢激活(I_(Ks))延迟整流钾电流、内向整流钾电流(I_(Kl))和瞬时外向钾电流(I_(to))的作用.方法:采用全细胞膜片箝技术记录豚鼠及大鼠心室肌细胞钾电流.结果:BTHP在 1-100 μmol/L的范围内以浓度依赖性方式阻滞I_(Kr)和I_(Ks),其中对I_(Kr)的IC_(50)为 13.5 μmol/L(95％可信限:11.2-15.8 μmol/L)而对 I_(Ks)的 IC_(50)则为 9.3 μmol/L(95％可信限:7.8-11.8 μmol/L).BTHP 30μmol/L时可使 I_(Kr)及I_(Kr,tail)分别降低31％±4％和36％±5％(n=6,P<0.01);使I_(Ks)及I_(Ks,tail)分别降低40％±6％和45％±15％(n=7,P<0.01);BTHP 5μmol/L可抑制大鼠心室肌细胞I_(to)电流,使电流幅值降低63％±6％(n=6,P<0.01),BTHP1-100μmol/L以浓度依赖性方式阻滞入I_(to),其 IC_(50)为 3.6 μmol/L(95％可信限:2.9-4.3μmol/L).但BTHP 200 μpmol/L对I_(Kl)基本无影响.结论:BTHP对I_(Kr)、I_(Ks)、I_(to)均有抑制作用,且其阻滞作用呈现出浓度依赖性特征.