Action Potential Upstroke Velocity Research Articles

Electrophysiologic effects of ambasilide (LU 47110), a novel class III antiarrhythmic agent, on the properties of isolated rabbit and canine cardiac muscle.

Electrophysiologic effects of ambasilide in canine isolated cardiac muscle driven at 1 Hz and in rabbit sinoatrial (SA) node preparations were determined by standard microelectrode technique. Ambasilide (10(-7)-10(-5) M) produced concentration-dependent increases in action potential duration measured at -80 mV (APD-80) repolarization time in canine ventricular muscle and in Purkinje fibers. APD measured at -20 mV (APD-20) was also increased in ventricular muscle, but it shortened with 10(-5) M in Purkinje fibers; at this concentration, there was a negligible change in the amplitude and the maximum upstroke velocity (Vmax) of action potentials and in the resting membrane potential. With the stimulation frequency between 30/min and 120/min, ambasilide (10(-5) M) produced a parallel increase in APD-80 as well as in APD-20 of ventricular muscle. In Purkinje fibers, the prolonging effect of ambasilide on APD-80 was more pronounced at lower stimulation frequency, whereas APD-20 shortened at all stimulation frequencies. Ambasilide at 10(-5) M also produced a prolongation of the effective refractory period (ERP) in Purkinje fibers. The drug produced no significant change in the frequency-dependent relationship between ERP and APD-80. A small but significant frequency-dependent inhibition of Vmax was noted in both ventricular muscle and Purkinje fibers. When the stimulus cycle length was reduced from 1,000 to 300 ms, Vmax in ventricular muscle decreased by 8.4 +/- 3.4% in control solution but by 22.6 +/- 5.6% after 10(-5) M ambasilide (n = 8, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Propagation of Electrical Activity in Ischemic and Infarcted Myocardium as the Basis of Ventricular Arrhythmias

Impulse Propagation in Ischemia. The disturbances in impulse propagation in the heart with regional ischemia and the heart with chronic infarction, which underlie the initiation and perpetuation of arrhythmias, are briefly reviewed. Evidence is presented that reentry is responsible for ventricular tachycardia in both conditions. During acute ischemia, reentrant excitation is characterized by unstable functional reentrant circuits, the properties of which are determined by the changes in transmembrane action potential. Tachycardia is caused by a single unstable reentrant circuit. Fibrillation ensues when a single circuit is broken up into many independent reentrant wavelets. In contrast, ventricular excitation during sustained monomorphic tachycardia in hearts with a healed infarct is characterized by stable reentrant circuits determined by the architecture of surviving myocardial cell bundles within the infarct. In acutely ischemic myocardium, conduction velocity is reduced to about half of the value in normal myocardium, due to the reduced action potential amplitude and upstroke velocity. After about 5–10 minutes ischemic cells become inexcitable at resting membrane potentials of ‐50 to ‐60 mV. An important characteristic of ischemic cells is the dependence of the action potential upstroke on cycle length mainly because of the markedly prolonged recovery from inactivation of the fast Na+ current in partially depolarized cells. Changes in transmembrane potentials do not occur homogeneously throughout the ischemic zone, and small differences in resting potential (associated with small differences in local K+ accumulation) of depolarized cells result in large local differences in refractory periods. The time dependence of refractoriness explains why an increase in sinus rate, or a single premature beat, may produce conduction block at certain sites, and allow conduction in adjacent areas, thus setting the stage for reentry. A decrease in electrical cell‐to‐cell coupling, which also is a factor in decreasing conduction velocity, only occurs after 15–20 minutes of ischemia. Its role in the type 1B arrhythmias, which coincide with the period when uncoupling begins, remains to be elucidated. The cellular electrophysiology of myocardial cells surviving in the subendocardium of infarcts in human hearts is close to normal. Conduction slowing may be caused by “zigzag” conduction along small bundles that are separated by fibrous tissue, and that merge and divide over small distances. (J Cardiovasc Electrophysiol, Vol. 3, pp. 77–87, February 1992)

Effects of Ritanserin on Transmembrane Action Potentials in Canine Purkinje Fibers

Ritanserin has been reported to be a potential antiarrhythmic. We studied the cellular electrophysiologic effects of ritanserin in canine Purkinje fibers. Ritanserin produced significant depressant effects on transmembrane action potentials elicited in canine Purkinje fibers. At concentrations of 10 and 40 mg/liter, ritanserin decreased Vmax (the upstroke velocity) of action potential in a dose-dependent fashion and shortened the duration of fast response action potential. These concentrations of ritanserin also reduced the amplitude and duration of the slow response action potentials induced in Purkinje fibers treated with isoproterenol (10(-5) M) and high K+ (22 mM). These in vitro results suggest that the cellular electrophysiologic actions of ritanserin may be due to its direct actions on cardiac sodium and calcium channels, which, in turn, may account for its antiarrhythmic effects.

Method and theory of monophasic action potential recording

MAP recordings have been at the cradle of cardiac electrophysiology but only recently, through safer and simpler technology, have gained wider access to clinical electrophysiology. In contrast to conventional electrode catheter recordings, MAP recording devices provide precise information not only of the local activation time but of the entire local repolarization time course as well. Although the MAP does not reflect the absolute amplitude or upstroke velocity of transmembrane action potentials, it delivers highly accurate information on the action potential duration and configuration, including early afterdepolarizations as well as relative changes in transmembrane diastolic and systolic potential changes. Based on available data, the MAP probably reflects the transmembrane voltage of cells within a few millimeters of the exploring electrode. MAPs can be recorded by catheter technique from the endocardial surface and by special probes from the epicardium in the operating room. The contact electrode technique is preferable over suction electrodes because it is safer and simpler to use in patients and because it produces more stable, longer-lasting signals. A modified contact MAP catheter incorporates pacing electrodes and permits simultaneous assessment of action potential duration and refractoriness. This not only facilitates the use of MAP catheters in routine electrophysiological studies but also is important for assessing the voltage-independent effects of antiarrhythmic drugs on refractoriness. MAP recordings offer the opportunity to study, in the in situ heart, a variety of pertinent electrophysiological phenomena including, for example, effects of cycle length changes and antiarrhythmic drugs on action potential duration or the role of afterdepolarizations in the genesis of triggered arrhythmias. Due to vigorous heart beating, movement artifacts may occur and need to be distinguished from true abnormalities in the action potential time course. With these limitations in mind, MAP recordings are a valuable addition to clinical electrophysiological studies.

Effect of glibenclamide on extracellular potassium accumulation and the electrophysiological changes during myocardial ischaemia in the arterially perfused interventricular septum of rabbit

The aim was to study the effects of glibenclamide on the rate of rise of extracellular potassium concentration ([K+]o) and the electrophysiological changes that occur during myocardial ischaemia. The study was performed in isolated, arterially perfused interventricular septa from the rabbit. Six septa were treated with glibenclamide 10(-6) mol.litre-1 and there were six untreated controls (vehicle only). [K+]o and electrophysiological variables were compared before and during a 30 min period of global zero flow ischaemia. Prior to ischaemia, the extracellular potassium concentrations measured using potassium sensitive valinomycin electrodes were similar in the control and glibenclamide groups being 4.0 (SEM 0.1) and 4.0 (0.1) mmol.litre-1 respectively. [K+]o rose during ischaemia in both groups, and at 30 min was 13.3 (0.7) mmol.litre-1 in the control group. The increase in the glibenclamide group was less marked, reaching 9.2 (0.5) mmol.litre-1 (p less than 0.0005; unpaired t test). Glibenclamide had no electrophysiological effects prior to ischaemia. However, during ischaemia the decrease in action potential amplitude, action potential duration (APD), maximum upstroke velocity of the action potentials (dV/dtmax), and the extent of resting membrane potential (Em) depolarisation were less in the glibenclamide group than in the controls. The effective refractory period (ERP) progressively shortened over the 30 min of ischaemia in both groups, to a similar extent. When taken in conjunction with the relative changes in action potential duration the degree of post-repolarisation refractoriness (ERP-APD) that developed was less in the glibenclamide group than in the controls. Glibenclamide attenuated the ischaemic rise in [K+]o, with preservation of both membrane potential and action potential amplitude, duration, and upstroke velocity together with less post-repolarisation refractoriness. These effects could be potentially antiarrhythmic in acute myocardial ischaemia.

Effects of Aprindine on Conduction Velocity and Vmax in Guinea‐Pig Papillary Muscles

One of the effects of antiarrhythmic drugs is the reduction of conduction velocity. Cable theory predicts that there is a nonlinear relationship between conduction velocity and upstroke velocity (Vmax) of action potential. By using conventional microelectrode techniques, aprindine-induced reduction of Vmax of action potential and conduction velocity in guinea-pig papillary muscles were measured. Aprindine-produced, use-dependent, and concentration-dependent changes in conduction velocity and the decline of square of conduction velocity was well fit by a single exponential. Time constants for square of conduction velocity were comparable to simultaneously measured time constants for effects of Vmax. At a concentration of 1 to 10 microM aprindine, onset changes between Vmax and conduction velocity had a log-linear relationship in a predicted fashion. Whereas, in the recovery process from aprindine-induced depression, slow recovery time course of conduction velocity was observed. In conclusion, in the presence of aprindine, only onset block of conduction velocity can be analyzed quantitatively in the relationship to observation on Vmax in vitro. These results suggested that in the presence of aprindine, the recovery of internal conductance may be slower than that of Vmax.

Increased Susceptibility to Hypoxia of Prolonged Action Potential Duration in Ventricular Papillary Muscles From Diabetic Rats

The action potential duration (APD) of ventricular muscles obtained from diabetic animals is reported to be prolonged. We studied the effect of varied periods of diabetes on APD prolongation using isolated ventricular papillary muscles from streptozocin-injected rats. We found that a diabetic period greater than 30 wk was necessary for the evolution of significant prolongation of APD. We then studied the effect of repeated hypoxia (PO2 40 mmHg) and normoxia (PO2 300 mmHg) on prolonged APD of diabetic muscles and compared the findings with those from control rats. Transmembrane potentials were recorded with conventional glass microelectrodes. Under normoxic conditions, the APDs of diabetic muscles were significantly prolonged, the maximum upstroke velocity of action potentials tended to be decreased, and the resting membrane potential was not changed significantly compared with controls. The first hypoxia (20 min) shortened the APD in both diabetic and control rats but more so in diabetic rats, thereby making the APD of diabetic rats virtually identical to the control rat APD during the hypoxia. On subsequent reoxygenation (30 min), these hypoxia-induced changes were almost recovered. The second hypoxia (20 min) produced more severe shortening of the APD in both muscle types, and the effect was again far greater in diabetic rats than controls, ending with a reversed sequence of APDs and the APD of diabetic muscles much shorter than the controls. Excessive shortening of APD in diabetic muscles during hypoxic conditions was speculated to be due to greater increases in the outward K+ current through ATP-regulated K+ channels that may be secondary to the more severe reduction of intracellular ATP concentrations in diabetic versus control hearts.

Electrophysiologic and Antiarrhythmic Actions of Pirmenol on Rabbit and Guinea Pig Cardiac Preparations

The electrophysiological and antiarrhythmic effects of pirmenol HCl were examined using the microelectrode technique applied to multicellular preparations and the suction-pipette whole-cell clamp method applied to ventricular myocytes from rabbit and guinea pig hearts. Pirmenol at 5 microM and higher doses suppressed the sinus node automaticity by depressing the slow diastolic depolarization without changing the maximum diastolic potential. Pirmenol at 1 microM and higher doses depressed the maximum upstroke velocity (Vmax) of action potentials and prolonged the action potential duration at 90% repolarization in atrial muscles and Purkinje fibers without affecting resting membrane potentials. Pirmenol at 5 microM depressed the early part of the plateau and lengthened the final repolarization of the action potentials in ventricular myocytes, of which effects were attributed to the depression of the calcium current and the delayed outward K+ current. Triggered tachyarrhythmias arising from delayed afterdepolarizations in papillary muscles and ventricular myocytes were markedly inhibited by 1-5 microM pirmenol. The drug changed the amplitude and appearance of the transient inward current in ventricular myocytes. These results suggest that pirmenol has electrophysiologic properties that could provide an antiarrhythmic action on various types of arrhythmias.

Negative Inotropic Effect of Ketamine in Rabbit Ventricular Muscle

The effect of ketamine on myocardial contractile force was examined in rabbit papillary muscles in order to determine the underlying mechanism of action of the anesthetic. Ketamine HCl (20 and 40 mg/L) inhibited rested-state contractions that are dependent on the transsarcolemmal influx of Ca2+ for activation and reduced the upstroke velocity of the slow action potential, which reflects Ca2+ influx through the slow Ca2+ channel. On the other hand, ketamine had a relatively small effect on potentiated-state contractions and no effect on rapid cooling induced contractures, both of which are activated by the release of Ca2+ stored in the sarcoplasmic reticulum. These results suggest that ketamine inhibition of transsarcolemmal Ca2+ influx plays a major role in the negative inotropic action of the anesthetic.

Rate dependence and supernormality in excitability of guinea pig papillary muscle

It is well known that in most cardiac tissues an increase in rate results in a decrease of excitability and, eventually, conduction block. We used microelectrode techniques to evaluate the rate and time dependence of excitation latency in 27 isolated guinea pig papillary muscles (GPPM). Latency was measured as the interval between the stimulus onset and action potential upstroke. When the intensity of current was just suprathreshold, prolongation of the basic cycle length (BCL) from 300 to 1,000 ms produced an increase in latency or failure of excitation. Such behavior was observed with extracellular as well as intracellular stimulation. Rate-dependent changes in latency were maximal during the first 10-20 s following the rate change and reached a steady state in approximately 200 s. Application of premature beats revealed the presence of a "supernormal phase" in which latency abbreviated. Strength-interval and strength-duration curves demonstrated that changes in excitability accurately paralleled those observed in latency. Hence, supernormal excitability at the end of the phase 3 repolarization was consistently observed in all ventricular muscle experiments. Deceleration-induced decrease of excitability was attended by hyperpolarization, increase of action potential upstroke velocity (Vmax) and action potential amplitude, and decrease in membrane resistance. Our data suggest that paradoxical rate-related changes of excitability in GPPM are the result of changes in the passive membrane properties. Under conditions of depressed conductivity, this particular behavior may account for the occurrence of bradycardia-dependent block.

Differential Analysis of the Frequency-Dependent Effects of Class 1 Antiarrhythmic Drugs According to Periodical Ligand Binding

The frequency-dependent block of cardiac sodium channels by class 1 antiarrhythmic drugs can be described by a periodical ligand binding process between drug molecules and channel binding sites. This predicts a linear relation between onset-rate constant of frequency-dependent block and diastolic interval as well as saturation of block with high stimulation rates. From both relationships, the binding kinetics (time constant, tau on) and saturation level of block (bdinf) can be estimated. This is exemplified for the frequency-dependent block (reduction of the maximal upstroke velocity of action potentials) induced by prajmaline (10(-6) M). In the same way, the frequency-dependent effects of 11 other class 1 drugs reported in the literature were analyzed and compared with each other. When the drugs are ranked with respect to their binding kinetics (tau on), there is a close relationship to the subclasses (1a, 1b, 1c), with 1b drugs exhibiting the fastest and 1c drugs the slowest kinetics. However, differences also exist in the saturation behavior of frequency-dependent block even within the same subclasses (1a and 1c). Thus, the class 1 drugs can also be subdivided in three other groups exhibiting clearly separated bands of block-frequency relations, with half-maximal saturation occurring at different stimulation rates. Our findings may have differential implications for the antiarrhythmic and proarrhythmic efficacy of class 1 drugs.

Effects of Isoflurane on Conduction Velocity and Maximum Rate of Rise of Action Potential Upstroke in Guinea Pig Papillary Muscles

This study was undertaken to determine whether isoflurane, a volatile anesthetic that is reported to possess a wide margin of cardiovascular safety, exerts electrophysiological effects on cardiac tissue. By use of standard microelectrode techniques, effects of isoflurane on the maximum rate of rise of action potential upstroke (Vmax) and conduction velocity were examined in guinea pig papillary muscles. Isoflurane decreased action potential amplitude and action potential duration in a concentration-dependent fashion. Isoflurane at 1.5 and 2.0 MAC decreased conduction velocity with as little influence on the maximum rate of rise of action potential upstroke as that exerted by halothane and enflurane. However, the effect of isoflurane in slowing intraventricular conduction was less than that of halothane and enflurane when compared at equi-MAC concentrations. Thus, isoflurane may be a safer anesthetic for the patients with intraventricular conduction abnormalities.

Ｉ群抗不整脈薬のＮａチャンネル抑制効果と陰性変力作用についての検討

The relationship between the negative inotropic effect and the effect on maximal upstroke velocity of action potentials (Vmax) induced by class 1 antiarrhythmic drugs [aprindine (A); cibenzoline (C); disopyramide (D); lidocaine (L); pirmenol (P); quinidine (Q)] was evaluated in the guinea-pig myocardium using electrophysiological techniques. Each drug reduced the force of contraction (Fc) and Vmax of fast action potentials dose-dependently. Tetrodotoxin and verapamil also decreased Fc in a dose-dependent manner. Class 1 an-tiarrhythmic drugs also reduced Vmax of the Ca-dependent slow response together with Fc. These drugs might be divided into three types according to the regression patterns of Fc. Type 1: The reduction of Fc was mainly due to Na channel blockade, resembling the pattern of tetrodotoxin (A). Drugs of this type show weaker negative inotropic than antiarrhythmic properties compared with drugs of types 2 and 3. Type 2: The reduction of Fc was predominantly due to Ca channel blockade, resembling the pattern of verapamil (Q). Type 3: Other type (C, D, L, P). This classification of class 1 antiarrhythmic drugs seems to be clinically useful in choice of drugs considering the patient's condition, such as cardiac function, and possible mechanism of arrhythmia.

Frequency- and voltage-dependent effects of AN-132, a new class I antiarrhythmic agent, on the maximum upstroke velocity (Vmax) of action potential upstroke in guinea pig ventricular muscles

Frequency- and voltage-dependent effects of AN-132, a new class I antiarrhythmic agent, on the maximum upstroke velocity (Vmax) of action potential upstroke in guinea pig ventricular muscles

Frequency- and Voltage-Dependent Effects of Recainam on the Upstroke Velocity of Action Potential in Rabbit Ventricular Muscle

The effects of recainam (Wy 42,362) on transmembrane action potentials were examined in isolated rabbit right ventricular papillary muscles. Recainam (3 x 10(-5) to 3 x 10(-4) M) caused a concentration-dependent decrease in the Vmax of the action potential. At 3 x 10(-4) M, there was a slight decrease in the amplitude of the action potential. The resting potential and the action potential duration were not affected. Use-dependent block of Vmax was tested over a wide range of pacing frequencies (from 0.1 to 3.0 Hz). At 1.0 Hz, recainam 10(-4) M produced exponential decreases in Vmax with a rate constant of 0.17 per action potential and 39.8% reduction at steady state. This use-dependent block was augmented at the higher stimulation frequencies. The time constant for the recovery of Vmax from use-dependent block (offset) was 17.2 s. In papillary muscles depolarized with 10 mM [K+]0, the use-dependent block was augmented but tonic block and the rates of onset and offset of the use-dependent block were similar to those in normally polarized preparations in 4 mM [K+]0. The curves relating membrane potential and Vmax in preparations stimulated at a low frequency (0.01 Hz) were not shifted by 10(-4) M recainam. These findings suggest that recainam is a specific sodium-channel blocker and has kinetically slow but potent affinity for the channel during action potentials. This selective binding during action potential was further augmented by depolarization and is likely to play a significant role in the control of ventricular arrhythmias by the drug.

Frequency- and Voltage-Dependent Effects of Recainam on the Upstroke Velocity of Action Potential in Rabbit Ventricular Muscle

Summary: The effects of recainam (Wy 42,362) on transmembrane action potentials were examined in isolated rabbit right ventricular papillary muscles. Recainam (3 × 10−5 to 3 × 10−4M) caused a concentration-dependent decrease in the JOURNAL/jcph/04.03/00005344-198904000-00017/OV0312/v/2021-02-06T190858Z/r/image-pngmax of the action potential. At 3 × 10−4M, there was a slight decrease in the amplitude of the action potential. The resting potential and the action potential duration were not affected. Use-dependent block of JOURNAL/jcph/04.03/00005344-198904000-00017/OV0312/v/2021-02-06T190858Z/r/image-pngmax was tested over a wide range of pacing frequencies (from 0.1 to 3.0 Hz). At 1.0 Hz, recainam 10−4M produced exponential decreases in JOURNAL/jcph/04.03/00005344-198904000-00017/OV0312/v/2021-02-06T190858Z/r/image-pngmax with a rate constant of 0.17 per action potential and 39.8% reduction at steady state. This use-dependent block was augmented at the higher stimulation frequencies. The time constant for the recovery of JOURNAL/jcph/04.03/00005344-198904000-00017/OV0312/v/2021-02-06T190858Z/r/image-pngmax from use-dependent block (offset) was 17.2 s. In papillary muscles depolarized with 10 mM [K+]0, the use-dependent block was augmented but tonic block and the rates of onset and offset of the use-dependent block were similar to those in normally polarized preparations in 4 mM [K+]0. The curves relating membrane potential and JOURNAL/jcph/04.03/00005344-198904000-00017/OV0312/v/2021-02-06T190858Z/r/image-pngmax in preparations stimulated at a low frequency (0.01 Hz) were not shifted by 10−4M recainam. These findings suggest that recainam is a specific sodium-channel blocker and has kinetically slow but potent affinity for the channel during action potentials. This selective binding during action potential was further augmented by depolarization and is likely to play a significant role in the control of ventricular arrhythmias by the drug.

Effects of Halothane and Enflurane on Conduction Velocity and Maximum Rate of Rise of Action Potential Upstroke in Guinea Pig Papillary Muscles

Using standard microelectrode techniques, the effects of halothane and enflurane on the maximum rate of rise of action potential upstroke (Vmax) and conduction velocity of excitation were compared with those of fast sodium channel blockers in isolated guinea pig papillary muscles. Lidocaine and tetrodotoxin decreased the square of the conduction velocity in proportion to the decrease in Vmax. In contrast, halothane and enflurane only slightly affected Vmax, but decreased the conduction velocity in a concentration-dependent manner. These results suggest that these volatile anesthetics affect conduction velocity by a mechanism different from that of fast sodium channel blockers. Caution should be used when these anesthetics are administered to patients receiving class 1 antiarrhythmic agents or who have pre-existing intraventricular conduction disease.

Effects of extract from a herbal drug, cnidium rhizome (senkyu), on contraction, heart rates and membrane potentials of isolated guinea pig atria

Effects of extract from a herb, Cnidium rhizome (Senkyu), on isolated guinea pig atria were investigated pharmacologically and electrophysiologically. The methanol extract from Cnidium rhizome decreased the contraction and slightly increased the heart rates of the isolated atria. Extracts from five other herbs, such as Japanese anglica root (Toki), Peony root (Shakuyaku), Moutan bark (Botanpi), Glycyrrhiza (Kanzo), Bupleurum (Saiko), affected neither the contraction nor the heart rates. The methanol extract from Cnidium rhizome was fractionated with chloroform and water fractions. The chloroform fraction exerted potent negative inotropic and chronotropic effects in isolated atria. The contraction was attenuated by two major components in the chloroform fraction, ligustilide and senkyunolide, but the heart rates were scarcely affected by these components. The chloroform fraction induced changes in resting potentials and configurations of normal action potentials recorded in the isolated left atria: the resting potentials were depolarized, and the upstroke velocity of the action potentials decreased. Neither ligustilide nor senkyunolide exerted such effects. The upstroke velocity of action potentials recorded in partially depolarized atria was reduced by the chloroform fraction as well as ligustilide and senkyunolide. The mechanisms underlying the effects of the extract from Cnidium rhizome were discussed.

Differential electrophysiological effects of amiodarone on ventricular muscle and Purkinje fibers in canine one-day-old myocardial infarction

1. We examined the electrophysiological effects of acute exposure to amiodarone (AM) on ischemic myocardium. 2. Regional myocardial ischemia was performed by occlusion on left anterior descending coronary artery in dog heart. 3. Conventional glass microelectrode techniques were used for electrophysiological investigation of regional ischemia. 4. The effects of AM on action potentials of subendocardial Purkinje fibers and ventricular muscle excised from ischemic area were studied and compared the findings with those obtained from non-ischemic area. 5. Acute exposure to AM, 4.4 × 10 −5 M, prolonged the total duration of action potential in the ischemic ventricular muscle and decreased the maximum upstroke velocity of action potentials significantly. 6. On the other hand, in the ischemic Purkinje fibers, AM produced no significant actions. 7. These findings suggest that AM's antiarrhythmic activity is, at least in part, due to its differential effects on repolarization of ischemic Purkinje fibers and ventricular muscle.

Tetrodotoxin-sensitive component in action potential plateau of guinea pig Purkinje fibers: Comparison with the papillary muscle

1. The effects of tetrodotoxin on action potentials of isolated guinea pig Purkinje fibers were examined and compared the findings with those obtained in the ventricular papillary muscle, by use of conventional microelectrode techniques. 2. Tetrodotoxin (5 × 10 −7–10 −5 M) decreased the amplitude, overshoot, and maximum upstroke velocity of action potentials of the Purkinje fibers, and shortened the duration of action potential at all levels of repolarization concentration- and stimulus cycle length-dependently. 3. The longer the stimulus cycle length, the greater the shortening by the drug of the action potential duration. 4. In particular, the plateau potential of the Purkinje fibers exposed to tetrodotoxin was remarkably depressed, and which occurred even in case of blockade of K + conductance, using tetraethylammonium. 5. On the other hand, a high concentration (10 −5 M) of tetrodotoxin did not significantly affect the papillary muscle action potentials. 6. These findings suggest that there is a tetrodotoxin-sensitive component of Na + current in plateau voltage range of the Purkinje fibers, but little in the papillary muscle, and that the component plays an important role to maintain the plateau of Purkinje fibers action potential.