Adrenaline and the plateau phase of the cardiac action potential

Summary Conduction block in heart cells by K⁺ rich, or Na⁺ depleted solutions can be overcome by adrenaline. In order to explain this phenomenon, the effect of adrenaline on the membrane resting and action potentials of cow Purkinje fibers was measured at various extracellular concentrations of Na⁺, K⁺ and Ca⁺⁺, in the presence of tetrodotoxin, Mn⁺⁺ and beta-receptor antagonists.It was found that adrenaline specifically increases the amplitude and duration of the plateau phase of the cardiac action potential. Plateu-like action potentials, without preceding Na⁺-spike, can be generated and conducted in an all-or-nothing way. In K⁺ rich solutions and under the influence of adrenaline, the depolarization proceeds in two steps. The first step corresponds to the Na⁺-spike. The second step or secondary depolarization corresponds to the plateau; it was not modified by changes of the membrane potential between –85 and –55 mV, or by reduction of extracellular Na⁺ ions, but was specifically blocked by Mn⁺⁺ ions and beta-receptor antagonists. Its amplitude increased by 17 mV for a tenfold change in extracellular Ca⁺⁺. Tetrodotoxin preferentially blocked the Na⁺-spike, but also slowed the rate of potential change during the secondary depolarization.The simplest explanation for the observed phenomena can be found in an increase of Ca⁺⁺ inward current under the influence of adrenaline. The existence of an inward Na⁺⁺ current, different in characteristics from the Na⁺ conductance during the fast upstroke, cannot be ruled out. Some data are in accord with a decrease in K⁺ conductance.     

The influence of passband limitation on the waveform of extracellular action potential

The duration of the extracellular action potential (EAP) in single neuronal recording has often been used as a clue to infer biochemical, physiological or functional substrate of the recorded neurons, e.g. neurochemical type. However, when recording a neuronal activity, the high-pass filter is routinely used to achieve higher signal-to-noise ratio. Signal processing theory predicts that passband limitation stretches the waveform of discrete brief impulse. To examine whether the duration of filtered EAP could be the reliable measure, we investigated the influence of high-pass filter both by simulation and unfiltered unit recording data from monkey dorsal raphe. Consistent with the findings in recent theoretical study, the unfiltered EAPs displayed the sharp wave without following bumps. The duration of unfiltered EAP was not correlated with that of filtered EAP. Thus the duration of original EAP cannot be estimated from filtered EAP. It is needed to reexamine the EAP duration measured for classifying the neurons whose activities were recorded under the passband limitation in the related studies.     

The prolongation of the action potential in mammalian ventricular muscle at rest

The conventional microelectrode technique was used to investigate the effect of long periods of rest (>10 s) on the action potential duration of mammalian ventricular muscle. The action potential duration increased as the rest period increased. This prolongation of the action potential was the greatest and the slowest in rabbit ventricle, was smaller and more rapid in guinea-pig ventricle, and was practically absent in rat ventricle. The prolongation of the action potential at rest was suppressed with aminazine and strophanthin. Low sodium concentration, lanthanum ions, ruthenium red and acidosis failed to suppress the slow prolongation. It is concluded that the slow prolongation of the action potential at rest is related to changes in the intracellular calcium content induced by a mechanism different from Na/Ca exchange.     

The generation of the cardiac action potential: After the first millisecond

After an initial, transient voltage-and time-dependent burst of sodium current (equivalent to that occurring in nerve), the membrane current of cardiac muscle reverses in sign to a maximum value that is orders of magnitude smaller than that seen in nerve. The membrane of cardiac muscle, rather than exchanging an increased permeability to sodium ions (Na⁺) for one to potassium ions (K⁺), appears to become relatively impermeable to a variety of ions. It is argued that in a tissue such as cardiac muscle where the time when the cell is active is comparable to that when it is quiescent, the current generated by the active electrogenic transport/exchange of Na⁺, K⁺, and Ca²⁺ must be comparable to the corresponding currents generated by the passive transport of these ions. Consequently, the complex voltage and time dependency of the membrane current on the time scale of repolarization and beyond is generated, at least in part, by the complex time and voltage dependency of these transport/exchange processes. Measurement of the electrochemical properties of such transport/exchange mechanisms must ultimately be made on the individual mechanisms in isolation, e.g., in artificial membrane systems, before their contribution to the generation of the cardiac action potential can be unequivocably determined.     

The role of the positive dynamic current on the action potential of cardiac Purkinje fibers.

The role of positive dynamic current (chloride current) on action potenitals of cardiac Purkinje fibers was studied. The removal of most extracellular chloride ions brought about a slowing of the repolarization process. The most prominent effect was noted onthe initial rapid repolization (phase 1) of the action potentials. Purkinje action potentials showed marked and consistent slowing of phase 1 with increasing rate of stimulation. The removal of (Cl-)0 caused marked loss of these frequency dependency in phase 1 and this effect was more prominent with slow rate of stimulation. The slopes of phase 2 and phase 3 also changed with varying frequency of stimulations but these changes were not affected much by chloride removal. Chloride conductance at the peak of the positive dynamic current increased linearly with membrane voltages from -20 mV up to +20 mV. Above this voltage, the conductance reached a plateau. A steady-state current voltage relationship was not influenced much by the chloride removal except slight decrease 031% in membrane conductance near the resting membrane potential. The increase in frequency of pulses produced marked decrease in the positive dynamic current in the voltage clamp experiments. These results suggest that the positive dynamic current mainly contribute to the electrogenesis of phase 1 in Purkinje action potentials.     

Influence of the surface EMG electrode on the compound muscle action potential

The recording characteristics of surface EMG electrodes were investigated. Compound muscle action potential (CMAP) and surface recorded motor unit action potentials were recorded from different muscles, using different surface electrode shapes and sizes. The CMAP was smaller for larger surface electrodes. This was more pronounced in smaller muscles. The CMAP was minimally affected by the geometry of the recording surface. With larger surface electrodes, shunting contributes to the reduction in MUAP amplitude. This is offset by a larger uptake area which gives a much smaller reduction in the CMAP amplitude for the larger muscles.     

50Hz滤波电路对心肌细胞自发动作电位波形分析的影响

目的：研究微电极放大器中的50Hz滤波电路对心肌细胞自发动作电位波形及各项参数的影响。方法：将心肌细胞自发动作电位经玻璃微电极、微电极放大器、微分器、A／D转换器输入微型计算机。在应用和不应用微电极放大器中50Hz滤波功能两种情况下,对心肌细胞自发动作电位波形进行比较分析。结果：在使用微电极放大器中50Hz滤波功能情况下,动作电位波形在0相严重失真,时程延长,除极化最大速度减小;复极化50％、90％的时间延长;其它参数无显著变化。结论：心肌细胞动作电位波形中含有50Hz信号成分,在研究心肌细胞动作电位信号时,不能使用50Hz滤波器。如果使用50Hz滤波器,会造成动作电位波形严重失真,影响实验结果。     

An automatic cardiac action potential duration meter.

The duration of a cardiac action potential (AP) is measured from the beginning of its upstroke to the end of its asymptotic repolarization phase: the end being given by a point in proportion to the AP amplitude. If the resting potential, AP amplitude, as well as the duration, alter simultaneously, frequent accurate measurements can be extremely tedious. A fully automatic AP duration meter has thus been constructed to cope with these difficulties while measuring within about 2% on a beat-to-beat basis. It is suitable either for brief sampling of AP durations when recording with microelectrodes, which may impale cells intermittently, or for continuous monitoring, as with suction electrodes on intact beating hearts in situ. For example, the device can faithfully track changes in duration during periods of regional myocardial ischemia in intact ventricles in situ while the AP alters its base line, upstroke velocity, amplitude, and duration.     

Effect of heterogeneities in the cellular microstructure on propagation of the cardiac action potential

Cardiac arrhythmias are initiated in regions that undergo cellular remodeling as a result of disease. Using a sub-cellular model of myocardium, we studied the mechanism of block caused by tissue microstructure remodeling: cell geometry [quantified as length/width (L/W) cell ratio] and cell-to-cell coupling (G(j)). Heterogeneities in cell L/W ratio and G ( j ) lead to block when excitability is reduced and the corresponding space constant λ (in the direction of propagation) increases by >40 %. Tissue architectures with elongated cells (i.e. large cell L/W ratios) that are better coupled (i.e. large G(j)) are less prone to block at sites of regional heterogeneities in cell geometry and/or cell coupling than tissue architectures consisting of cells with smaller L/W ratios and/or poorer coupling. Whether an increase in tissue anisotropic ratio (ANR) is arrhythmogenic or not depends on the cellular mechanism of the increase: ANR leads to an increased risk of block when G(j) decreases, but to a decreased risk of block when cell L/W ratio increases. Our findings are useful to understand the mechanisms of block in cardiac pathologies that result in tissue architecture remodeling.     

The mechanism of Ca2+ action on the healing-over process in mammalian cardiac muscles: a kinetic analysis

The effect of Ca2+ concentration and temperature on the recovery of membrane potential after investigating lesions using sucrose-gap technique in the guinea-pig papillary muscles were studied. At certain temperatures, this recovery showed increased accerelation with increasing Ca2+ concentration. The relation between rate constant of the recovery and Ca2+ concentration was quite similar to that of the reaction between an enzyme and substrate. This relationship could be expressed by the equation Y = xn(Km + xn), where Y is the normalized rate constant and x the Ca2+ concentration. The coefficient, n, was evaluated by performing Hill's plot. The value of n largely changed between 1 and ca. 2 at 32 degrees C--37 degrees C. The input resistance fell at the instant of formation of a lesion and started to rise with recovery of membrane potential. The resistance change after lesion formation was also observed in the potassium-Tyrode's solution in which Na+ was substituted with K+. The concentration-rate relationship of Ca2+ in the healing-over seems to indicate that Ca2+ binds to some molecules in the junctional membrane and produce a structural change of intercalated disc which brings about the healing-over. The large change of n suggests that Ca2+ has a cooperative action in the healing-over process, or alternatively that the state of membrane lipids has some effect on the process.