镉对豚鼠心脏乳头状肌动作电位及收缩力的影响

应用细胞内固定微电极技术,观察了不同浓度CdCl_2对豚鼠右心室乳头状肌快、慢反应AP及Fc的影响.结果表明20μmol/L CdCl_2对快反应APA及V_(max)无显著影响,但却抑制Fc;100和500μmol/L对上述各参数均呈抑制作用.各种剂量的CdCl_2对慢反应电位均可降低APA及V_(max),抑制Fc,缩短APD_(50)及APD_(90),对抗CaCl_2所致的正性频率作用.提示低剂量Cd使心肌细胞兴奋收缩脱耦联.可能有抗心肌Ca~(2+)流效应.     

甲氧普胺对豚鼠缺氧与非缺氧心肌动作电位和收缩力的影响

甲氧普胺10μmol/L使乳头状肌动作电位0相上升最大速率(Vmax)降低,100μmol/L并使收缩力(FC)低,300μmol/L时动作电位时程(APD_(20),APD_(90))缩短,30μmol/L使缺氧心肌动作电位的Vmax降低,APD_(20)缩短。     

赛庚啶对豚鼠乳头状肌的收缩性与动作电位的影响

Cyp对豚鼠孔头状肌有浓度依赖性负性肌力作用,提高浴液钙浓度此作用减弱,对高K~+除极后ISO恢复的收缩抑制作用更强。较高浓度的Cyp使频率依赖性正阶梯现象取消和翻转。对乳头状肌AP,Cyp浓度依赖性地使APD_(20),APD_(50),APD_(90)和ERP缩短。灌流液中Ca~(2+)降低或升高分别使该作用增强或减弱,K~+的改变对其作用影响较小。提示Cyp对豚鼠乳头状肌收缩性和AP的作用可能主要是抑制心肌跨膜Ca~(2+)内流所致。     

胺碘酮对离体心肌的负性肌力作用

对离体左,右心房肌,胺碘酮(Ami)1～100μmol·L~(-1)均有负性肌力作用,30μmol·L~1明显抑制心肌静息后收缩,正阶梯和成对刺激效应,1～10μmol·L~1使苯福林,异丙肾上腺素,组胺和CaCl_2正性肌力作用的量效曲线呈非竞争性拮抗作用,心肌动作电位和收缩力同步记录发现,Ami 30μmol·L~1减弱心肌收缩,延长APD,但对平台期和V_(max)无影响.故Ami的负性肌力作用可能是抑制心肌细胞外Ca~(2+)内流和细胞内Ca~(2+)释放所致,并非选择性阻滞心肌α,β和H_2受体以及电压依赖性钙通道引起 .     

甲基莲心碱对豚鼠心肌电—机械活动的影响

甲基莲心碱(Nef)0.1mM使豚鼠右心室乳头状肌的收缩力降低68. 3％,使动作电位APA和Vmax分别从112±5mV,240±37V/s降低到97±9 mV和86±25V/s;APD_(50),APD_(90)和ERP分别从173±23ms,205±17ms和201±16ms延长到201±26ms,239±28ms和249±23ms。Nef 1-200μM浓度依赖性地延长APD_(50),APD_(90)和ERP,降低Vmax和收缩力。30μM Nef能明显对抗10μM乙酰胆碱缩短豚鼠左心房APD的作用。结果提示,Nef对心肌Na~+,K~+,Ca~(2+)的跨膜转运均有抑制作用。     

呋喃苯胺酸对蟾蜍心肌电与机械活动的影响

使用浮置式细胞内微电极方法,结合肌力换能器,观察了呋喃苯胺酸(Furosemide,Fur6×10~(-4)mol/L)对蟾蜍离体心肌电及机械活动的影响。结果显示:Fur作用20min时使右心房收缩力(FC)增加到147.50%;动作电位幅值(APA)、O相上升最大速率(V_(max))及动作电位时程(APD_(50))分别增加到108.69%、106.58%及103.45%。对APD_(25)、APD_(90)及窦性周长(SCL)无明显影响,Fur的正性肌力作用能被维拉帕米(Verapamil,Ver2.2×10~(-7)mol/L)所取消。实验结果提示Fur具有促进Ca~(2+)内向电流的作用。     

蛇床子素对豚鼠离体回肠和结肠带的作用

以豚鼠离体回肠和结肠带为标本,观察蛇床子素(Ost)的作用与Ca~(2+)的关系。结果表明:Ost和钙拮抗剂Ver产生剂量依赖性抑制乙酰胆碱(ACh)、组胺及KCl所致回肠条或结肠带的收缩;非竞争性拮抗CaCl_2累积量—效曲线,pD_2分别为4.41±0.15,7.0±0.2。Ost 100μmol/L和Ver 1μmol/L均能对抗小剂量Ca~(2+)所致结肠带收缩,但被加入较大量Ca~(2+)所取消。Ost和Ver均能抑制ACh诱导的依内钙性收缩,不影响依外钙性收缩。结果提示Ost具有钙拮抗作用,其作用方式与Ver类似。     

心肌细胞钙通道的特性与调节

<正> 可兴奋细胞的跨膜Ca~(2+) 内流对维持其细胞功能具有极其重要的意义,它参与许多重要生理过程,诸如:肌肉收缩、递质释放、激素分泌、酶活性调节和膜离子通透性等。有关Ca~(2+)在心肌兴奋—收缩耦联过程中的作用正在深入而广泛地进行研究。 心肌细胞在静息状态时,细胞内游离的Ca~(2+)浓度约在10~(-7)mol/L,兴奋时则增高到10~(-6)～10~(-5)mol/L范围,此改变一方面是因胞外Ca~(2+)(10~(-3)mol/L)进入     

磷酸羟基喹哌对豚鼠右室乳头状肌动作电位和收缩力的影响

本文采用常规微电极技术,研究了HPQP对豚鼠乳头状肌电和机械活动的影响。HPQP在10μmol/L以上是浓度依赖性地抑制收缩力,延长动作电位时程和有效不应期,低浓度时仅抑制V_(max),浓度在100μmol/L以上时可使动作电位幅度降低。在30μmol/L时能对抗乙酰胆碱缩短左房肌动作电位时程的作用。HPQP 100μmol/L能对抗哇巴因诱发的后振荡电位。结果提示:HPQP能非特异性地抑制Na~+,K~+和Ca~(2+)的跨膜转运。     

赛庚啶对离体犬心肌肌质网Ca~(2+),Mg~(2+)—ATP酶活性和~(45)Ca~(2+)摄取功能的影响

当赛庚啶浓度在8×10~(-6)mol/L～2×10~(-4)mol/L之间时,该药对正常犬心肌肌质网Ca~(2+),Mg~(2+)—ATP酶活性几乎没有影响,仅在10~(-3)mol/L时对该酶活性才有一定的抑制作用(抑制率为39.85%,P<0.01)。正常犬心肌肌质网的~(45)Ca~(2+)摄取过程有明显的时间依赖性,至第30 min,其~(45)Ca~(2+)摄取量可达312.79±22.25 nmol/mg protein.赛庚啶对心肌肌质网的~(45)Ca~(2+)摄取有一定的抑制作用,其IC_(50)为1.94×10~(-4)mol/L。     

Positive inotropic effect of cycloprotobuxine-A on isolated guinea pig myocardium

Cycloprotobuxine-A (CPB-A) 0.1-100 mumoles/L produced positive inotropic effects in left and right atria in a concentration-dependent manner. CPB-A 30 mumoles/L enhanced post-rest contraction, augmented the response of left atrium to increase in stimulating frequency, and increased the developing tension evoked by paired pulse stimulation. By taking simultaneous recordings of action potentials and contractile force of papillary muscles, it was found that CPB-A 30 mumoles/L increased the contractile force and prolonged the action potential duration at 50% of depolarization. It is concluded that the positive inotropic effect of CPB-A on myocardium may be associated with an increase in transsarcolemmal influx of calcium as well as an augmentation of the amount of calcium released from intracellular stores.     

药根碱对离体豚鼠心房的作用

药根碱使豚鼠左房收缩力和+dF/dt依浓度地增加,-dF/dt/df下降,收缩及舒张时间延长,并提高肾上腺素诱发的左房自律性降低乳头状肌的自律性。延长左房功能性不应期,降低右房自搏频率.药根碱能明显增强心肌的正性阶梯现象,对双脉冲刺激及静息后增强效应无影响。实验表明,药根碱对心肌的作用与小檗碱相似。其正性肌力作用与外Ca~(2+)内流有关,而不涉及细胞内Ca~(2+)的释放。     

吡喹酮及其对映异构体对离体大鼠心房肌生理特性的影响

吡喹酮(praziquantel,PQT)对心肌生理特性的影响有立体选择性。(-)-PQT对离体大鼠左心房的正性肌力作用的效能和强度均比(+)-PQT和(±)-PQT小。用维拉帕米可明显减弱PQT及其对映异构体的正性肌力作用。在浓度为100μmol/1时,PQT及其对映异构体对离体大鼠右心房均有负性频率作用,而当30μmol/1时仅(+)-PQT对频率有明显影响。它们尚可诱发右心房心律失常,其发生率以(+)-PQT最高,(-)-PQT最低,(±)-PQT居中。(+)-和(±)-PQT可明显缩短左房不应期。(+)-PQT还可明显降低左房自律性,而(-)-PQT对不应期,自律性均无影响。     

呋喃二氢吡啶Ⅰ对豚鼠心肌收缩力及动作电位的影响

呋喃二氢吡啶I(FDP I)呈浓度依赖性地抑制豚鼠心肌收缩力,IC_(50)为1.62μmol·L~1,并能抑制心肌静息后增强效应.成对刺激及正阶梯现象的收缩幅度,离体心乳头状肌细胞跨膜电位实验表明:FDPI 1.0、4.0μmol·L~1能缩短动作电位之APD_(30)·APD_(50),APD_(90),硝苯碇(Nif)0.1.1.0,4.0μmol·L~1亦能缩短APD,但两药在所试浓度范围内,对APA和V_(max)均无明显影响。     

Alinidine reverses the descending staircase of isolated rat atria by an antimuscarinic action

Summary Contractile force of isolated atria from most mammalian species increases with the rate of electrical stimulation, resulting in an ascending staircase. In contrast, in the rat, contractile force decreases with increasing rate of stimulation (descending staircase). The bradycardic and antianginal drug alinidine (5.7–91.2 mol/l) reversed the descending staircase to ascending by a positive inotropic effect at higher stimulation rates. Maximal positive inotropy was obtained with 45.6 mol/l, a concentration which also caused maximal bradycardia in spontaneously beating atria. Concentrations of 1 mol/l of the antimuscarinic compounds atropine as well as the quarternary salt ipratropium bromide also reversed the descending staircase of rat atria. Addition of alinidine did not cause any further increase in force of contraction under these conditions. Addition of 1 mol/l physostigmine to isolated left atria from guinea pigs for blockade of acetylcholinesterase decreased contractility at all stimulation rates, but did not change the ascending character of the staircase. Alinidine antagonized the negative inotropic effect of physostigmine. The known antimuscarinic action of alinidine was quantified in electrically driven (0.25 Hz) left rat atria by antagonism of the negative inotropic effect of oxotremorine (0.01–10 mol/l). Alinidine acted as a strictly competitive antagonist with a pA₂ of 5.82. In isolated papillary muscle from guinea pigs, pretreated with reserpine for depletion of catecholamines, carbachol (0.1–3000 mol/l) exerted positive inotropic effects. Alinidine antagonized also this effect in a competitive fashion with a pA₂ value of 5.58. Investigations of the specific antimuscarinic compounds pirenzepine, methoctramine and AF-DX 116 in these models indicate that the negative inotropic effect in atria is mediated by M_2a-receptors while the positive inotropic effect in papillary muscle is mediated by either the M_2e-receptor or a yet unidentified muscarinic subreceptor.It is concluded that the descending staircase of electrically stimulated rat atria is due to the release of acetylcholine as well as to the short duration of its action potential which decreases further upon muscarinic stimulation, thus leading to a compromise of excitation-coupled calcium influx and negative inotropy, particularly at higher stimulation rates. Therefore, antimuscarinic drugs including alinidine reverse the descending staircase. Under physiological conditions of impulse generation and in the absence of vagal activity an ascending staircase is to be expected in rat atria as well.     

Diamide: positive inotropic effect in isolated atria and inhibition of Na+/Ca2+ exchange in cardiomyocytes

The influence of frequency of stimulation and external calcium on the positive inotropic response of guinea-pig left atria to diamide and the inhibitory action on Na+/Ca2+ exchange activity of rat cardiomyocytes by this oxidant of sulphhydryl groups have been investigated. Diamide (50-500 microM) induces a concentration-dependent positive inotropic effect which is more pronounced when atria are driven at 1.0 Hz rather than at 0.5 and 0.1 Hz, and are bathed in 2.72 mM rather than in 1.36 mM external calcium. A decrease in the positive inotropic effect at 35 degrees C with respect to 29 degrees C is also observed. In addition, diamide in positive inotropic concentrations (100-300 microM) significantly reduces Na+/Ca2+ exchange activity and cytoplasmic glutathione levels in adult rat cardiomyocytes. The thiol reducing agent dithiothreitol either reverses or prevents diamide effects both in isolated atria and cardiomyocytes, suggesting that the actions of diamide are correlated to its property to oxidize sulphhydryl groups to disulphides. In view of the functional importance of Na+/Ca2+ exchange in myocardial contractility, it is proposed that diamide may increase the heart force of contraction by an inhibition of the sarcolemmal Na+/Ca2+ exchange activity.     

Effects of Ca2+ channel antagonists and ryanodine on H1-receptor mediated electromechanical response to histamine in guinea-pig left atria

Summary Effects of organic Ca²⁺ channel antagonists, Ni²⁺ and ryanodine on the electrophysiological and positive inotropic responses to histamine were examined in isolated guinea-pig left atria. Histamine increased force of contraction, prolonged action potential duration (APD) and hyperpolarized the membrane in a concentration-dependent manner. Histamine at a concentration of 1 mol/l produced a dual-component positive inotropic response composed of an initial increasing phase (initial component) and a second an late developing, greater positive inotropic phase (second component), whereas causing monophasic changes in APD and resting potential. The electrophysiological and dual-component positive inotropic effects induced by histamine were antagonized by chlorpheniramine (1 mol/l) but not by cimetidine (10 mol/l), indicating that both effects are exclusively mediated by H₁-receptors. The positive inotropic response to 1 mol/l histamine was changed by the pretreatment with nifedipine (1 mol/l) and nisoldipine (1 mol/l). In the presence of these dihydropyridines, the second component was almost completely abolished, while the initial component was hardly affected. On the other hand, verapamil (3 mol/l) and diltiazem (10 mol/l) failed to modify the multiphasic inotropic response to histamine. None of the Ca²⁺ channel antagonists affected the histamine-induced APD prolongation. In the presence of Ni²⁺ at a concentration of 0.3 mmol/l, at which it produced no negative inotropic action, the second component of the positive inotropic effect of histamine was specifically suppressed whereas the histamine-induced APD prolongation was unaffected. Preferential attenuation of the second component was also observed in the presence of 30 nmol/l ryanodine. However, the electrophysiological alterations caused by histamine remained unchanged. These results suggest that in guinea-pig left atria the H₁-receptor-mediated prolongation of APD seems unlikely to be due to enhancement of the slow inward Ca²⁺ current. Conversely, the increased Ca²⁺ influx as a result of the APD prolongation may contribute to the second component of the positive inotropic effect of histamine. Dihydropyridine Ca²⁺ channel antagonists, Ni²⁺ and ryanodine are all capable of inhibiting the second component, but do so possibly via different mechanisms, implying the complicated mechanisms underlying the H₁-receptor-mediated positive inotropic effect.Send offprint requests to Y. Hattori