Ionic currents and action potentials in rabbit,rat, and guinea pig ventricular myocytes

Summary Distinct differences exist in action potentials and ionic currents between rabbit, rat, and guinea pig ventricular myocytes. Data obtained at room temperature indicate that about half of the rabbit myocytes show prominent phase 1 repolarization and transient outward current. Action potentials in guinea pig ventricular myocytes resemble those from rabbit myocytes not exhibiting phase 1 repolarization; and guinea pig myocytes do not develop transient outward current. Rat ventricular action potentials are significantly shorter than those from rabbit and guinea pig ventricular myocytes. Unlike rabbit and guinea pig myocytes, rat ventricular myocytes also exhibit a prominent phase 1 and lack a well defined plateau phase during repolarization. All rat ventricular myocytes exhibit a transient outward current which can be best fitted by a double exponential relation. There are no significant differences between the amplitude, voltage dependence and inactivation kinetics of the inward calcium currents observed in rabbit, rat and guinea pig. The steady-state current-voltage relations between –120 mV and –20 mV, which mostly represent the inward rectifier potassium current are similar in rabbit and guinea pig. The amplitude of this current is significantly less in rat ventricular myocytes. The outward currents activated upon depolarization to between –10 and +50 mV are different in the three species. Only a negligible, or absent, delayed rectifier outward current has been observed in rabbit and rat; however, a relatively large delayed rectifier current has been found in guinea pig. These large interspecies variations in outward membrane currents help explain the differences in action potential configurations observed in rabbit, rat, and guinea pig.     

源于右室流出道的室性心律失常的电生理机制研究

目的探讨右室流出道(RVOT)室性心律失常的发生机制。方法采用全细胞膜片钳技术记录RVOT和右室(RV)心肌细胞的动作电位及离子流,对比分析动作电位及离子流的特性。结果RVOT心肌细胞动作电位表现出复极离散度较RV大。在单细胞电流的记录中,RVOT心肌细胞的瞬时外向钾电流离散度较RV心肌细胞大。在稳态电流中,RVOT心肌细胞的非特异性阳离子流(NSCC)小于RV心肌细胞的NSCC,甚至某些RVOT心肌细胞缺乏NSCC,与之对应的是心肌细胞较长的动作电位时程(APD)并记录到早期后除极(EAD)。当激活NSCC后,可使RVOT心肌细胞较长的APD缩短。激活的NSCC可以消除在RVOT记录到的EAD。结论RVOT心肌细胞的复极离散度和APD的离散大,此易导致折返性心律失常的发生。NSCC较小或缺如是RVOT心肌细胞APD延长,并且产生EAD的原因。     

Influence of thyroid hormone levels on the electrical and mechanical properties of rabbit papillary muscle

We have examined the influence of chronic in vivo alterations of thyroxine levels on the electrophysiological and mechanical properties of rabbit ventricular papillary muscles measured in vitro. Marked changes in the repolarization phase of the action potential and the time to peak tension of isometric twitches were observed when thyroid hormone levels were increased above or decreased below normal. The time to peak tension was consistently shorter than normal in hyperthyroid and longer than normal in hypothyroid preparations. In hypothyroid preparations the action potential duration was greater than that of controls at all stimulation frequencies tested (0.1 to 1.0 Hz). In hyperthyroid preparations, the repolarization phase consisted of an initial phase of fast repolarization to membrane potential values between -20 and -40 mV followed by a plateau. The early phase of repolarization persisted at all stimulation frequencies tested (0.1 to 1.0 Hz) but the plateau component increased markedly as the stimulation frequency was decreased. The early phase of repolarization was markedly reduced in the presence of 4-aminopyridine. These results suggest that thyroxine levels may modulate the kinetics of a transient outward current which in rabbit papillary muscle normally is responsible for the frequency dependence of action potential duration. Action potential amplitude, maximum rate of rise, resting membrane potential, and peak isometric twitch tension were not markedly different between the three classes of preparations. A second depolarizing response occurred in all hyperthyroid preparations at low stimulation frequencies (0.1 to 0.4 Hz) but not in control or hypothyroid preparations. This second depolarizing response, which was eliminated by D-600 treatment, was similar to the calcium-dependent slow action potentials recorded in other cardiac preparations. These two component action potentials could represent either intrinsic single cell activity, or a re-entry wave of depolarization which results from nonhomogeneous excitation.     

低渗性肿胀对豚鼠心室肌细胞动作电位及延迟整流钾电流的影响

观察单个豚鼠心室肌细胞动作电位和主要复极期电流延迟整流钾电流(IK)的变化,探讨急性心肌缺血再灌注室性心律失常发生的离子机制。采用全细胞膜片钳记录技术,观察低渗液(200mOsm/kg)灌流胶原酶分离的单个豚鼠心室肌细胞发生肿胀后的动作电位各参数的变化,同时记录IK及其快、慢两种激活成分(IKr及IKs)的变化。结果:低渗液灌流后心室肌细胞迅速发生肿胀,动作电位幅度(APA)、静息膜电位(RMP)及阈电位水平无明显变化;而动作电位时程(APD)在600,1000和3000ms三种基础起搏周长(BCL)刺激时均缩短(P<0.05),尤以APD复极达50%和90%时缩短更为明显。APD生理性频率适应性消失且离散度增大。低渗性肿胀状态下IK电流幅度在3000ms长去极化保持时间(主要成分为IKs)刺激时从1134.33±150.17pA增加至1621.98±234.95pA(P<0.001,n=10);而在100ms短去极化保持时间(主要成分为IKr)刺激时从693.44±96.44pA降低至294.06±71.79pA(P<0.05,n=8);并且使IK的IV曲线向上移位。结论:低渗性肿胀的心室肌细胞IK特别是IKs的增加是引起APD缩短的重要因素,是急性心肌缺血再灌注室性心律失常发生的离子机制之一。     

锌对心肌保护作用机理的探讨

应用电镜、电子示踪技术和立体计量测试法，从形态学上观察异丙基肾上腺素对心肌膜系统的影响及锌的保护作用，同时应用标准玻璃微电极技术和微机实时分析方法，研究异丙基肾上腺素致心肌损伤及锌对心肌保护作用的机理。实验结果表明：异丙基肾上腺素可引起心肌细胞膜系统损伤，此时心肌细胞的去极化和复极化过程均发生改变；经锌前处理后，心肌损伤程度明显减轻，心肌细胞的复极化过程得到明显改善。锌对心肌的保护作用，主要是通过阻断心肌细胞膜慢通道、减少平台期钙离子内流、防止细胞内钙超载来实现。     

Autoantibodies against the beta1 adrenoceptor from patients with dilated cardiomyopathy prolong action potential duration and enhance contractility in isolated cardiomyocytes.

Autoantibodies against the beta1-adrenoceptor (beta1-AAB) from patients with dilated cardiomyopathy (DCM) increase the beating frequency of cultured neonatal rat cardiomyocytes. This effect is accompanied by only a small increase in cAMP production. Here we have investigated whether beta1-AAB affect electrophysiological properties and cell shortening of isolated cardiomyocytes by interacting with the beta1-adrenoceptor. Beta1-AAB were obtained during immunoadsorption of patients with DCM and were used for experiments in isolated myocytes cultured from neonatal rat hearts, or freshly isolated from adult rat ventricles or from human right atria. The unselective beta -adrenoceptor agonist (-)-isoprenaline was studied for comparison. Immunoglobulin G (IgG) antibodies increased the spontaneous beating frequency of neonatal rat cardiomyocytes to a lesser degree than (-)-isoprenaline, but both effects were maximum and stable after 2 min. In rat ventricular and human atrial myocytes, IgG increased action potential duration (APD) in a concentration-dependent manner with larger effects on late than on early repolarization phases. Similar effects were obtained with purified beta1-AAB, whereas flow through of the chromatography column was ineffective. (-)-isoprenaline prolonged APD to the same extent during plateau and late phase of repolarization. beta1-AAB increased L-Type Ca2+ current in correspondence with the prolongation of APD. The effects of beta1-AAB and (-)-isoprenaline on APD were strongly attenuated after preincubation of the myocytes with the selective beta1-adrenoceptor antagonist (-)-bisoprolol. In addition, beta1-AAB increased cell shortening in ventricular myocytes from adult rat hearts. Beta1-AAB enhancing the beating frequency of cultured cardiomyocytes, increase L-Type Ca2+ current, APD and contractility in freshly isolated cardiomyocytes mediated via beta1-adrenoceptors. These effects may contribute to beta1-adrenoceptor-mediated cardiotoxicity in heart failure.     

Ionic basis for membrane potential changes induced by hypoosmotic stress in guinea-pig ventricular myocytes

OBJECTIVE: Causal relation between changes in action potentials and activation of several ionic currents during hypoosmotic challenge was investigated. METHODS: We recorded changes in membrane potentials and currents during hypotonic stress in guinea-pig ventricular myocytes using whole-cell patch-clamp technique. RESULTS: Exposure of ventricular myocytes to hypotonic solution (0.6 T) caused initial prolongation ( approximately 107% of control) of action potential duration at 90% repolarization (APD(90)) in 65% of examined myocytes. Later shortening (approximately 75% of control) of APD(90) and depolarization of resting potential (RP) (approximately 4 mV) developed in all cells. Initial prolongation of APD(90) in hypotonic solution was mainly caused by transient activation of Gd(3+)-sensitive non-selective cation (NSC) current. Late changes after approximately 180 s in hypotonic solution were sustained increase in slow component of delayed rectifier K(+) current (I(Ks)) in all cells, and activation of I(Clswell) in 40% of cells. Prevention of APD(90) shortening by chromanol, a selective blocker of I(Ks), was seen in about 40% of myocytes due to short APD in our experimental conditions. Application of 1 mM anthracene-9-carboxylic acid (9-AC) partially inhibited APD shortening in three of seven cells. Depolarization of RP was unaffected by the above-mentioned drugs, but was dependent on [K(+)](o). CONCLUSIONS: Initial prolongation followed by later shortening of APD in hypotonic solution are mostly caused by different sequences of NSC, I(Ks) and I(Clswell) currents activation. Depolarization of RP in hypotonic solution is probably due to dilution of subsarcolemmal K(+) concentration and/or change in permeability ratio for Na(+) and K(+).     

Calcium current restitution in mammalian ventricular myocytes is modulated by intracellular calcium

Restitution of the conventional L-type calcium current (ICa) was studied in dog or guinea pig ventricular myocytes to understand its time course and regulation. Whole-cell ICa free of other overlapping currents was recorded with a suction pipette. The intracellular environment was varied by intracellular dialysis. The properties of ICa were similar in dog and guinea pig ventricular myocytes, except that the amplitude of ICa was larger in the latter (2.2 +/- 0.5 nA in guinea pig cells and 0.9 +/- 0.2 nA in dog cells, n = 8 for both). In both types of cells during restitution a holding voltage (Vh) negative to -50 mV induced a transient increase in ICa above the control level (ICa overshoot). This overshoot was inhibited by substituting barium for calcium, lowering [Ca]0, increasing intracellular calcium buffering capacity, ryanodine (1-2 microM), or caffeine (10 mM). The overshoot peaked 30-100 msec after repolarization from the conditioning depolarization and gradually declined over the following 2-3 seconds. During the overshoot, although the amplitude of ICa was larger its half-time of decay was longer than the control. The maximum overshoot occurred following a conditioning step to plateau voltages and it was decreased by prolonging the conditioning step from 50 to 100 or 500 msec. It is concluded that intracellular calcium regulates restitution of the L-type calcium channels in mammalian ventricular myocytes and that the sarcoplasmic reticulum is involved in this process.     

异丙肾上腺素诱导钙离子激活氯电流在兔心房肌细胞电重构中的意义

目的探讨在异丙肾上腺素(ISO)诱导下,兔心房肌细胞L型钙电流(ICa,L)与钙离子激活氯电流(ICl,Ca)之间的变化以及心房肌细胞动作电位(AP)复极相的特征性变化。方法用酶解法分离兔心房肌细胞。全细胞膜片钳技术记录所需离子电流和AP。结果(1)在记录到ICa,L后,加入1μmol/LISO5min,可引出一个非常明显的外向电流,并随着钳制电压的增加,ICa,L峰值逐步减小,而外向电流峰值逐步增加。3mmol/L的4氨基吡啶对这种外向电流不起作用。但150μmol/L的4,4异二硫氮氐2,2′二磺酸可抑制这种外向电流,而几乎只剩下ICa,L。200μmol/L钙通道阻滞剂CdCl2可阻断ICa,L和外向电流。表明该实验在加入ISO后引出最初的内向电流ICa,L之后,被激活的外向电流为ICl,Ca,诱发率为91.67%(P<0.05)。(2)在电流钳制下引出AP后,1μmol/LISO可使正常情况下的AP平台没有,AP呈三角形的尖锥峰形。AP时程的APD50和APD90明显缩短,与对照组相比,分别缩短了80.46%和71.87%,差异有统计学意义。3mmol/L的4氨基吡啶对该AP三角形的尖锥峰几乎没有作用;但4,4异二硫氮氐2,2′二磺酸(150μmol/L)使AP平台得以恢复,与对照组相比,差异无统计学意义。表明正常的心房肌细胞在ISO作用下,与形成AP复极相有关的1相和2相的离子转运发生了改变,Ito2对心房肌细胞AP1相形成起着重要作用。结论兔心房肌细胞在原本只被记录ICa,L情况下,经ISO干预后,细胞内某离子浓度发生了改变,细胞膜上离子通道的开放发生了重新变化,钙离子激活Cl-通道,Ito2表现出了明显优势,使AP时程明显缩短,AP呈三角形的尖锥峰形而无明显平台,心房肌细胞发生了离子通道电重构。离子通道电重构可能起自于ISO诱导的L型钙通道激活氯离子通道开放增加,并且ICa,L降低。这可能揭示离子通道电重构发生的一种机制。也为探讨实验性房性心律失常发生机制提供了又一证据。     

Sinusoidal stimulation of myocardial tissue: effects on single cells

INTRODUCTION: Cardiac tissue subjected to sinusoidal stimulus is characterized by action potentials (APs) that have extended plateau phases, sustained for the duration of the stimulus. Extended action potential durations (APDs) are beneficial because they disrupt wandering wavelets in the fibrillating heart. To investigate the mechanisms by which periodic stimulus affects cardiac tissue, particularly the development of sustained depolarization, computer simulations of single cardiac cells exposed to alternating current (AC) are performed. METHODS AND RESULTS: Two modes of stimulation of the cell are examined: external field stimulation and transmembrane current injection. Several membrane models, including Luo-Rudy I and II, are used in the simulations. External AC field stimuli increase the APD of the single cell. The extended plateau of the cellular AP is characterized by periodic oscillations that are 1:2 phase locked with the applied stimulus. This specific behavior is due to the variations in stimulus magnitude and polarity along the cell border, which elicit opposite electrical responses from the cell sides. These pointwise responses are averaged in the macroscopic cellular response and result in sustained oscillatory depolarization that lasts for the duration of the stimulus. In contrast, the cell undergoing current injection does not develop an extended APD. CONCLUSION: The simulations demonstrate that variation of membrane potential within a cell is of paramount importance to the formation of an extended AP plateau in response to AC stimulation.     

In vitro characteristics of repolarization abnormality--a possible cause of arrhythmias

When membrane potential (Vm) remains at depolarized levels for prolonged intervals, quiescence and/or repetitive activations occur. In situ such events would be associated with arrhythmias. One way for such a state to occur is abnormal delay of repolarization leading to marked prolongation of action potential (AP) duration (APD). We studied canine Purkinje fibers in which abnormal AP prolongation had been induced by hypoxic, acidic Tyrode's with or without epinephrine, or by Ni++. AP's exhibited a prolonged secondary plateau with or without early afterdepolarizations (EAD's); they were up to ten minutes in duration. With programmed stimulation, APD's displayed a markedly exaggerated interval dependence with slight increases in diastolic interval causing transitions from normal to abnormal and very long AP's. Normalization of AP's occurred during prolonged rapid pacing trains and only gradually returned to abnormality after cessation of pacing. We also induced EAD's via programmed stimulation at plateau Vm levels. Repolarization could be brought on abruptly via these stimulus-induced EAD's; in certain instances trains of EAD's were required. The above characteristics of the state for which the term "repolarization failure" seems appropriate may have implications for in situ arrhythmias, e.g. in "Torsade de Pointes" ventricular tachycardia.     

Quantitative Prediction of Body Surface Potentials from Myocardial Action Potentials Using a Summed Dipole Model

This paper demonstrates quantitatively, using streamlined mathematics, how the transmembrane ionic currents in individual cardiac muscle cells act to produce the body surface potentials of the electrocardiogram (ECG). From fundamental principles of electrostatics, anatomy, and physiology, one can characterize the strength of apparent dipoles along a wavefront of depolarization in a local volume of myocardium. Net transmembrane flow of ionic current in actively depolarizing or repolarizing tissue induces extracellular current flow, which sets up a field of electrical potential that resembles that of a dipole. The local dipole strength depends upon the tissue cross section, the tissue resistivity, the resting membrane potential, the membrane capacitance, the volume fraction of intracellular fluid, the time rate of change of the action potential, and the cell radius. There are no unknown, “free” parameters. There are no arbitrary scale factors. Body surface potentials are a function of the summed local dipole strengths, directions, and distances from the measuring points. Calculations of body surface potentials can be made for the scenarios of depolarization (QRS complex), repolarization (T wave) and localized acute injury (ST segment shifts) and agree well with experimentally measured potentials. This simplified predictive dipole theory provides a solution to the forward problem of electrocardiography that explains from a physiological perspective how the collective depolarization and repolarization of individual cardiac muscle cells create body surface potentials in health and disease.

自发性高血压大鼠左心室流出道自发性电活动的特征

利用玻璃微电极细胞内记录方法 ,记录了自发性高血压大鼠 (SHR)和Wistar鼠左心室流出道自发性慢电位和自发性快电位的特征。结果发现 ,SHR自发性快电位的动作电位时程 (APD)、复极至 5 0 %时间 (APD50 )和复极至 90 %的时间 (APD90 )均明显长于Wistar鼠 (P <0 0 1) ;SHR的自发放电频率 (RPF)明显慢于Wistar鼠 (P <0 0 5 )。结果提示 :SHR左心室流出道自发性的快电位和慢电位均表现为APD、APD50 和APD90 的延长 ,RPF减慢     

Synchronized repolarization after defibrillation shocks. A possible component of the defibrillation process demonstrated by optical recordings in rabbit heart.

BACKGROUND. It is currently believed that defibrillation shocks act primarily by stimulating excitable myocardium to abolish wave fronts. Recent studies have shown that shocks applied during pacing not only stimulate excitable myocardium but also prolong the depolarization and refractoriness of myocardium already in a depolarized state. This study investigates the effects of shocks on fibrillation action potentials. METHODS AND RESULTS. Recordings of membrane action potentials free of shock artifact were obtained using the voltage-sensitive dye WW781 during defibrillation of isolated rabbit hearts. These records showed that the shocks caused an additional phase of depolarization beginning with an initial rapid depolarization of the optical signal followed by a slow phase of repolarization. This occurred throughout all phases of the fibrillation action potential from just after completion of the upstroke to a time of near maximal repolarization. Defibrillation shocks, however, had the additional effect of causing the myocardium to repolarize at a constant time after the shock regardless of its prior electrical activity--the constant repolarization time response. This effect was not dependent on the presence of D600 (methoxyverapamil) or continuous coronary perfusion. It was accompanied by a similar constancy in the return of myocardial excitability. Recordings taken from multiple adjacent recording sites also showed a constant repolarization time among them. CONCLUSIONS. A simple model of reentry is used to illustrate how the constant repolarization response, in addition to wave front termination and refractoriness extension, could play a role in the successful termination of fibrillation by electrical shock.     

Heterogeneous distribution of the two components of delayed rectifier K+ current: a potential mechanism of the proarrhythmic effects of methanesulfonanilideclass III agents.

OBJECTIVE: To elucidate the regional difference of the K+ current blocking effects of methanesulfonanilide class III agents. METHODS: Regional differences in action potential duration (APD) and E-4031-sensitive component (IKr) as well as -insensitive component (IKs) of the delayed rectifier K+ current (IK) were investigated in enzymatically isolated myocytes from apical and basal regions of the rabbit left ventricle using the whole-cell clamp technique. RESULTS: At 1 Hz stimulation, APD was significantly longer in the apex than in the base (223.1 +/- 10.6 vs. 182.7 +/- 14.5 ms, p < 0.05); application of 1 microM E-4031 caused more significant APD prolongation in the apex than in the base (32.5 +/- 6.4% vs. 21.0 +/- 8.8%, p < 0.05), resulting in an augmentation of regional dispersion of APD. In response to a 3-s depolarization pulse to +40 mV from a holding potential of -50 mV, both IK tail and IKs tail densities were significantly smaller in apical than in basal myocytes (IK: 1.56 +/- 0.13 vs. 2.09 +/- 0.21 pA/pF, p < 0.05; IKs: 0.40 +/- 0.15 vs. 1.43 +/- 0.23, p < 0.01), whereas IKr tail density was significantly greater in the apex than in the base (1.15 +/- 0.13 vs. 0.66 +/- 0.11 pA/pF, p < 0.01). The ratio of IKs/IKr for the tail current in the apex was significantly smaller than that in the base (0.51 +/- 0.21 vs. 3.09 +/- 0.89; p < 0.05). No statistical difference was observed in the voltage dependence as well as activation and deactivation kinetics of IKr and IKs between the apex and base. Isoproterenol (1 microM) increased the time-dependent outward current of IKs by 111 +/- 8% during the 3-s depolarizing step at +40 mV and its tail current by 120 +/- 9% on repolarization to the holding potential of -50 mV, whereas it did not affect IKr. CONCLUSIONS: The regional differences in IK, in particular differences in its two components may underlie the regional disparity in APD, and that methanesulfonanilide class III antiarrhythmic agents such as E-4031 may cause a greater spatial inhomogeneity of ventricular repolarization, leading to re-entrant arrhythmias.     

Responses of the Transmembrane Potential of Myocardial Cells during a Shocks

Responses of Transmembrane Potential During a Shock. Introduction: The purpose of this investigation was to study the transmembrane potential changes (δV_m) during extracellular electrical field stimulation. Methods and Results: V_m was recorded in seven guinea pig papillary muscles in a tissue hath by a double-barrel microelectrode with one barrel in and the other just outside a cell while shocks were given across the bath. The short distance (15 to 30 μm) between the two microelectrode tips and alignment of the tips parallel to the shock electrodes eliminated the shock artifact. Following ten SI stimuli, an S2 shock field created by a 10-msec square wave was delivered during the action potential plateau or during diastole through shock electrodes 1 cm on either side of the tissue. Four shock strengths creating field strengths of 1.7 ± 0.1, 2.9 ± 0.2, 6.1 ± 0.6. and 8.8 ± 0.9 V/cm were given for the same impalement. Both shock polarities were given at each shock strength. For shocks delivered during the action potential plateau, the magnitudes of the peak δV_m caused by the above four potential gradients were 21.1 ± 8.2, 33.6 ± 13.6, 49.9 ± 24.2, and 52.3 ± 28.0 mV (P < 0.05 among the four groups) for the shocks causing depolarization and 37.9 ± 14.2,56.6 ± 16.4,83.1 ± 19.4. and 92.9 ± 29.1 mV (P < 0.05 among the four groups) for the shocks causing hyperpolarization. Though δV_m increased as potential gradients increased, the relationship was not linear. The magnitude of hyperpolarization was 1.9 ± 0.5 times that of depolarization when the shock polarity was reversed (P < 0.05). As potential gradients increased from 1.7 ± 0.1 to 8.8 ± 0.9 V/cm, the time constant of the membrane response decreased significantly from 3.5 ± 1.8 to 1.6 ± 0.7 msec for depolarizing shocks and from 6.0 ± 3.1 to 3.4 ± 1.9 msec for hyperpolarizing shocks (P < 0.01 vs depolarizing shocks). For shocks delivered during diastole, hyperpolarizing shocks induced triphasic changes in V_m during the shock, i.e., initial hyperpolarization, then depolarization, followed again by hyperpolarization. Conclusion: During the action potential plateau, the membrane response cannot be represented by a classic passive RC membrane model. During diastole, activation upstrokes occur even during hyperpolarization caused by shocks creating potential gradients between aproximately 2 and 9 V/cm.     

锌对豚鼠心肌细胞跨膜电位及钙通道活动的影响

目的探讨锌对动作电位平台期的作用及锌与慢钙通道之间的关系。方法借助常规玻璃微电极技术和微机实时分析的方法,观察低钙、异搏定和锌对豚鼠心室乳头肌细胞电活动的作用。结果低钙、异搏定和锌对静息电位（ＲＰ）和动作电位峰值（ＡＰＡ）均无明显作用,但可使超射（ＯＳ）和最大去极化速率（Ｖｍａｘ）降低;并影响心肌细胞的复极化过程,使动作电位时程显著缩短,尤其是复极达峰值电位５０％和１０％的时程差（ＡＰＤ５０－１０）缩短更明显。结论实验结果表明,低钙、异搏定和锌均主要通过影响动作电位平台期而使动作电位时程缩短,动作电位时程的缩短与平台期的缩短是一致的,可见锌能阻断慢通道、降低钙离子内向电流,锌具有异搏定样慢通道阻滞剂的作用     

Reversal of repolarization gradient does not reverse the chirality of shock-induced reentry in the rabbit heart

INTRODUCTION: Two hypotheses have been proposed to explain the mechanisms of vulnerability and related failure of defibrillation therapy: the cross-field-induced critical point hypothesis and the virtual electrode-induced phase singularity hypothesis. These two hypotheses predict the opposite effect of preshock repolarization on the chirality (direction of rotation) of shock-induced reentry. The former suggests its reversal upon reversal of repolarization, whereas the latter suggests its preservation. The aim of this study was to determine, by reversing the repolarization sequence, which of the mechanisms is responsible for internal shock-induced arrhythmia in the Langendorff-perfused rabbit heart. METHODS AND RESULTS: We used high-resolution optical mapping to assess the chirality of postshock reentry in 11 hearts. Hearts were paced at a coupling interval of 300 msec at various sites around the field of view (13.5 x 13.5 to 16.5 x 16.5 mm). Cathodal monophasic implantable cardioverter defibrillator shocks (-100 V, 8 msec) were applied during the T wave from a 10-mm coil electrode placed into the right ventricular cavity. We used 3.5 +/- 0.8 different pacing sites per heart. Change in direction of repolarization did not result in change of chirality. Chirality was constant in all 11 hearts despite the complete reversal of activation and repolarization patterns. However, the position of resulting vortices depended on transmembrane polarization gradient inverted delta Vm and amplitude of negative polarization Vm (deexcitation). Stronger gradients and deexcitation produced earlier epicardial break excitation (P = 0.04 and P < 0.0001, respectively). CONCLUSION: Virtual electrode-induced phase singularity mechanism underlies internal shock-induced arrhythmia in this model.     

Effects of quinidine on plateau currents of guinea-pig ventricular myocytes

Effects of quinidine on membrane currents forming the plateau of action potentials were studied using an isolated single ventricular cell from guinea-pig hearts. Quinidine (5 mg/l) produced a fall and shortening of the early part of the plateau, and delayed its later part and final repolarization, without changes in resting membrane potential. Application of quinidine caused a reversible depression of the peak Ca2+ current by about 30% of the control. Delayed outward K+ current, iK, also decreased to less than 20% of the control. Thus, an outward tail current upon repolarization to -40 mV from depolarizing voltage steps of the plateau ranges became inward. Current values at the end of 200 ms pulses in response to voltage steps to -60-0 mV were always positive and were not changed by the drug. The inward current elicited at potentials negative to resting potential level, also, decreased by 13% to 23% of the control in the presence of the drug, but the effect was not reversible upon wash-out of the drug. These results suggest that quinidine causes a non-specific depression of inward rectifier K+ current, iK1, with minor degree but has little effect on the window sodium current. Therefore, changes in the action potential repolarization produced by quinidine can be explained by its effects on both calcium current and delayed outward K+ current.     

异丙肾上腺素对犬心房肌细胞动作电位及L型钙电流的影响

目的研究两种浓度的异丙肾上腺素(Isoproterenol,ISO)对犬心房肌细胞(AP)及L型钙电流(ICa,L)的作用。方法采用离体灌注和消化的方法获取心房肌细胞,用全细胞记录技术记录单个心房肌细胞AP以及ICa,L。结果低浓度ISO(10nmol/L)可延长APD,可使90%AP时程(APD90)延长34.4%,并降低AP平台期水平。高浓度ISO(1μmol/L)可减少APD,APD90减少32.1%。两种浓度的ISO均可诱发AP后除极及触发活动。10nmol/L和1μmol/LISO分别增加ICa,L36.7%和49.3%。结论两种浓度的ISO对心肌细胞ICa,L均有促进作用,Ca2+内流引起的肌浆网Ca2+释放可能是房性心律失常的发生机制之一。