白藜芦醇对家兔窦房结起搏细胞的电生理效应(英文)

目的为探讨白藜芦醇是否能成为抗心律失常药,研究了其对窦房结起搏细胞的电生理效应。方法应用细胞内微电极方法记录家兔窦房结起搏细胞的动作电位。结果白藜芦醇(30~120μmol.L-1)显著降低窦房结起搏细胞的动作电位幅度、零相最大上升速率(Vmax)、舒张期除极速率和起搏放电频率。而对最大舒张期电位和90%复极化的时间无明显作用。预先应用L型钙通道开放剂Bay-K-8644(0.5μmol.L-1)灌流窦房结10 min可阻断白藜芦醇(60μmol.L-1)对起搏细胞的上述电生理效应。而应用超极化激活电流阻断剂氯化铯(2 mmol.L-1)加钾通道阻断剂四乙铵(20 mmol.L-1)或应用一氧化氮(NO)合酶阻断剂-LNAME(0.5 mmol.L-1)灌流窦房结标本10min对白藜芦醇(60μmol.L-1)的电生理效应没有明显影响。结论白藜芦醇能抑制家兔窦房结起搏细胞的自发活动,此效应可能与其通过非NO依赖性途径抑制钙离子内流有关。     

双苯氟嗪对家兔窦房结起搏细胞电生理的影响

用细胞内微电极技术研究双苯氟嗪(3-30 μmol·L^-1)对家兔窦房结起搏细胞电生理特性的影响. 结果表明,双苯氟嗪浓度依赖性地降低窦房结起搏细胞的动作电位幅度(APA),0相最大上升速率(V_max), 舒张期除极速率(VDD)和自发搏动速率(RPF), 但在所用浓度范围内对最大舒张电位和50%复极化时程均无显著影响.双苯氟嗪显著抑制高Ca²⁺(4 mmol·L^-1)和Bay K8644(0.5 μmol·L^-1)所致的VDD和RPF加速.结果提示,双苯氟嗪降低家兔窦房结起搏细胞APA,V_max, VDD和RPF的作用可能与其抑制Ca²⁺内流有关.     

胍丁胺对兔窦房结起搏细胞的电生理效应(英文)

目的:研究胍丁胺(Agm)对兔窦房结起搏细胞的电生理效应及其作用机制。方法:应用玻璃微电极方法。结果:Agm不仅能剂量依赖地抑制兔窦房结起搏细胞的V_(max),APA和VDD,RPF;而且能延长APD_(90);idazoxan能明显抑制Agm的电生理效应;而L-NAME不能影响Agm的电生理效应;提高灌流液中的Ca~(2 )浓度可对抗Agm的作用;ATP-敏感性钾通道开放剂(lemakalim)可部分拮抗Agm延长APD_(90)的作用。结论:Agm对窦房结的电生理效应由肾上腺素能α-受体和咪唑啉受体介导,并与Ca~(2 )内流和K~ 外流减少有关。     

胍丁胺对兔窦房结起搏细胞的电生理效应

AIM: To study the electrophysiologic effects of agmatine (Agm) on pacemaker cells in sinoatrial (SA) node. METHODS: Parameters of action potential (AP) in SA node were recorded using intracellular microelectrode technique. RESULTS: Agm not only slowed down the amplitude of action potential (APA), maximal rate of depolarization (Vmax), velocity of diastolic (phase 4) depolarization (VDD), and rate of pacemaker firing (RPF), but also prolonged 90% duration of action potential (APD90) in a concentration-dependent manner. The effects of Agm (10 mmol.L-1) could be blocked completely by pretreatment with idazoxan (0.15 mmol.L-1), an alpha 2-adrenergic receptor (alpha 2-AR) and imidazoline receptor (IR) antagonist. Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 1 mmol.L-1), an NOS inhibitor, did not affect the electrophysiologic effects of Agm on pacemaker cells in SA node. Elevation of Ca2+ concentration (5 mmol.L-1) in perfusate antagonized the effects of Agm (10 mmol.L-1). Lemakalim (Lem, 30 mumol.L-1), an opener of ATP-sensitive potassium channels, partially inhibited the prolonging effect of Agm on repolarization. CONCLUSION: The electrophysiologic effects of Agm on pacemaker cells in SA node were likely attributed to the reduction in calcium influx and potassium efflux and mediated by alpha 2-AR and IR.     

莫索尼定对小鼠生殖系统的影响

莫索尼定为一高度选择性咪唑啉-Ⅰ型受体激动剂,通过激动延髓腹外侧核(RVLM)-Ⅰ型咪唑啉受体使外周交感神经的活性降低,从而舒张血管和减少外周阻力血管阻力使血压下降。左心室舒张末期和收缩末期容量减少,然而心率、心搏出量、心输出量、肺动脉压基本上没有改变[1-3],但莫索尼     

乳酸酸中毒对兔窦房结优势起搏细胞动作电位的影响

目的：观察乳酸酸中毒对兔窦房结优势起搏细胞自律性、传导性等电生理的影响。方法：应用玻璃微电极技术,在不缺氧的条件下,观察了17只兔离体窦房结优势起搏细胞在5mmol/L,10mmol/L和15mmol/13种浓度的乳酸酸中毒条件下动作电位的变化。结果：随着乳酸浓度的增加,动作电位参数发生进行性变化,至15mmol/L第30min时,4相自动除极速率及0相除极速率分别降低了48％及38％（均P＜0．05）,窦房结优势起搏细胞自主起搏周期长度延长了53％（P＜0．05）,复极90％,50％,30％的动作电位时程分别延长了25％,39％及41％（均P＜）．05）。结论：乳酸到中毒可降低窦房结优势起搏细胞自律性,延缓其传导性,并使动作电位时程延长。     

腺苷三磷酸通过P1受体影响兔窦房结起搏细胞电生理活动(英文)

目的:研究腺苷三磷酸(ATP)对兔离体窦房结起搏细胞动作电位的作用,分析相关受体。方法:利用细胞内微电极技术记录兔离体窦房结细胞跨膜电位。结果:ATP 0.1-3.0mmol/L浓度依赖性减慢窦房结自发搏动速率16％-43％,降低舒张期除极速率33％-67％,增大动作电位幅值6％9％,加快最大除极速率30％-76％,APD_(50)和APD_(90)分别缩短7％-12％和6.3％-9％,等浓度ATP、腺苷二磷酸(ADP)和腺苷(Ado)的效应相比时,各组间无显著性差异,尿苷三磷酸(UTP)和α,β-meATP对动作电位各参数均无影响,P1受体拮抗剂氨茶碱(0.1mmol/L)显著拮抗ATP和Ado的作用(P<0.05),且拮抗程度相同,P2受体拮抗剂反应兰2 (0.05mmol/L)不影响ATP的作用(P<0.05)。结论:兔窦房结不存在功能性P2X,和P2Y_2受体,ATP对兔窦房结的作用主要通过其降解产物Ado,由P1受体介导而发挥。     

Electrophysiologic effect of dipfluzine on pacemaker cells in sinoatrial node of rabbits

用细胞内微电极技术研究双苯氟嗪（３－３０μｍｏｌ·Ｌ－１）对家兔窦房结起搏细胞电生理特性的影响．结果表明,双苯氟嗪浓度依赖性地降低窦房结起搏细胞的动作电位幅度（ＡＰＡ）,０相最大上升速率（Ｖｍａｘ）,舒张期除极速率（ＶＤＤ）和自发搏动速率（ＲＰＦ）,但在所用浓度范围内对最大舒张电位和５０％复极化时程均无显著影响．双苯氟嗪显著抑制高Ｃａ２＋（４ｍｍｏｌ·Ｌ－１）和ＢａｙＫ８６４４（０．５μｍｏｌ·Ｌ－１）所致的ＶＤＤ和ＲＰＦ加速．结果提示,双苯氟嗪降低家兔窦房结起搏细胞ＡＰＡ,Ｖｍａｘ,ＶＤＤ和ＲＰＦ的作用可能与其抑制Ｃａ２＋内流有关．     

关附乙酯对兔窦房结起搏细胞的作用

目的:研究关附乙酯(DGFA)对窦房结起搏细胞电生理学的影响.方法:采用细胞内微电极技术记录家兔窦房结动作电位(AP)参数.结果:DGFA不仅能够减慢自主性激发频率(SFF),平均复极化速率(MRR),舒张期除极化速率(RDD),而且以剂量依赖性方式延长窦房结舒张期间隔(DI)和动作电位时程(APD).此外,DGFA显著降低除极化最大速率(MRD),并伴有动作电位幅度(APA)的轻微下降,对最大舒张电位(MDP)无显著作用.DGFA降低自主性激发频率的作用不受阿托品(0.05 mg/L)的影响.结论:DGFA这些作用可能是通过减少钙离于内流及钾离子外流产生的,而非阻断M受体.     

蝙蝠葛碱和利多卡因对人心房和兔房室结细胞动作电位及窦房结功能的影响

蝙蝠葛碱(Dau)浓度依赖性抑制病人心房纤维及家兔房室结细胞APA,V_(max),减慢SR,病人心房纤维SP_4亦明显降低,并延长房室结细胞APD_(90)。利多卡因(Lid)在治疗浓度对AP各参数无明显影响,100μmol/L时明显降低病人心房纤维APA,V_(max),30μmol/L时降低兔房室结细胞V_(max)和SP_4。在两种标本,SR均呈减慢趋势。Dau明显延长家兔SACT,对SNRT,CSNRT,SNRTI和HR无明显影响,但与Lid合用可使CSNRT明显延长。提示Dau明显抑制窦房结传导功能,与Lid合用时使其自律性亦明显降低。Dau抑制心房纤维和房室结细胞AP可能为其临床上有效地治疗室上性快速型心律失常的主要电生理基础。     

Negative chronotropic actions of endothelin-1 on rabbit sinoatrial node pacemaker cells

1. The effects of endothelin-1 (ET-1) on sinoatrial (SA) node preparations of the rabbit heart were studied by means of whole-cell clamp techniques.
2. ET-1 at 1 nM slowed the spontaneous beating activity and rendered half of the cells quiescent. At a higher concentration of 10 nM, the slowing and cessation of spontaneous activity were accompanied by hyperpolarization.
3. In voltage-clamp experiments, ET-1 decreased the basal L-type Ca²⁺ current (I_Ca(L)) dose-dependently with a half-maximal inhibitory concentration (EC₅₀) of 0.42 nM and maximal inhibitory response (E_max) of 49.5%. The delayed rectifying K⁺ current (I_K) was also reduced by 33.2±11.1% at 1 nM. In addition, an inwardly rectifying K⁺ current was activated by ET-1 at higher concentrations (EC₅₀=4.8 nM). These ET-1-induced changes in membrane currents were abolished by BQ485 (0.3 μM), a highly selective ET_A receptor antagonist.
4. When I_Ca(L) was inhibited by ET-1 (1 nM), subsequent application of 10 μM ACh showed no additional decrease in I_Ca(L), suggesting the involvement of cyclic AMP in the effects of ET-1 on I_Ca(L). In contrast, 1 nM ET-1 further decreased I_Ca(L) in the presence of 10 μM ACh, suggesting that ET-1 activates some additional mechanism(s) which inhibit I_Ca(L). The ET-1-induced I_Ca(L) inhibition was abolished by protein kinase A inhibitory peptide (PKI, 20 μM) or H-89 (5 μM). However, the I_Ca(L) inhibition was not affected by methylene blue (10 μM), suggesting a minor role for cyclic GMP in the effect of ET-1 under basal conditions.
5. ET-1 failed to inhibit I_Ca(L) when the pipette contained GDPβS (200 μM). However, incubation of the cells with pertussis toxin (PTX, 5 μg ml⁻¹, >6 h) only reduced the ET-1-induced inhibition to 21.5±9.5%, whereas it abolished the inhibitory effect of ACh on I_Ca(L).
6. Intracellular perfusion of 8-bromo cyclicAMP (8-Br cyclicAMP, 500 μM) attenuated, but did not abolish the inhibitory effect of ET-1 on I_Ca(L). This 8-Br cyclicAMP-resistant component (17.5±14.4%, n=20) was not affected by combined application of 8-Br cyclicAMP with 8-bromo cyclicGMP (500 μM), ryanodine (1 μM) or phorbol-12-myristate-13-acetate (TPA; 50 nM).
7. In summary, ET-1 exerts negative chronotropic effects on the SA node via ET_A-receptors. ET-1 inhibits both I_Ca(L) and I_K, and increases background K⁺ current. The inhibition of I_Ca(L) by ET-1 is mainly due to reduction of the cyclicAMP levels via PTX-sensitive G protein, but some other mechanism(s) also seems to be operative.

     

氯化汞对培养乳鼠心肌细胞和家兔窦房结电活动的影响

氯化汞对培养乳鼠心肌细胞和家兔窦房结电活动的影响１马欣荆伟庆赵松珍２（西安医科大学药理学教研室，２第一附属医院神经科，西安７１００６１）汞是一种微量元素，长期大剂量接触可产生心脏毒性作用，如引起不同类型的心律失常［１］．但是，汞对心血管系统的毒性机理...     

辣椒素对家兔窦房结起搏细胞的电生理效应

目的:研究辣椒素对离体家兔窦房结起搏细胞的电生理效应及其作用机制。方法:应用经典玻璃微电极方法。结果:辣椒素(10 μmol/L)使窦房结起搏细胞的零相最大上升速度(V_(max))由(2.4±0.5)V/s降至(1.7±0.2)V/s(P<0.05);舒张期除极速度(VDD)由(91±34)mV/s降至(70±30)mV/s(P<0.01);起搏放电频率(RPF)由(186±14)beat/min降至(162±10)beat/min(P<0.01);最大舒张电位(MDP)绝对值由(49±3)mV降至(44±2)mV(P<0.01);动作电位幅度(APA)由(55±4)mV降至(49±4)mV(P<0.05)。复极化90％时间(APD_(90))则由(149±21)ms延长至(167±27)ms(P<0.01)。应用辣椒素受体阻断剂钌红(10 μmol/L)对辣椒素的上述电生理效应无影响。提高灌流液中钙离子浓度(5 mmol/L)以及应用L型钙通道开放剂Bay-K-8644(0.5μmol/L)均可抑制辣椒素对起搏细胞的电生理效应。β-肾上腺素能受体激动剂异丙肾上腺素(20 nmol/L)可逆转辣椒素所引起的除极化时间延长和MDP的降低。结论:辣椒素对家兔窦房结细胞有负性变时作用,这些效应可能与其抑制钙离子内流及/或钾离子外流有关,而非由辣椒素受体介导。