Effects of bivalent cations on post-rest adaptation in guinea-pig heart muscle

In isolated papillary muscles of guinea-pig hearts, the inotropic effects of bivalent cations, Ca2+, Ba2+, Sr2+, and Ni2+, were investigated during post-rest adaptation in order to study their individual action on excitation-contraction coupling. Upon exposure to each cation studied, the force of contraction was transiently enhanced, whereas the steady state force was influenced differently: it increased with Ca2+, Ba2+ and Sr2+ and was depressed by Ni2+. The transmembrane action potentials (measured at 90% repolarization) were slightly prolonged by Sr2+ and even more by Ba2+, and were shortened by Ca2+ and Ni2+. After 10 min rest, the post-rest contractions consisted of a late peak (PII) that was enhanced in high Ca2+-solution an by Sr2+. Ni2+ and Ba2+ depressed PII and during adaptation to pre-rest controls an early peak of contraction (PI) prevailed. There was no simple relation between post-rest adaptation of force and the duration of action potential in the presence of the bivalent cations tested. During post-rest adaptation the two components of contraction can be separated. The results are interpreted in terms of a model of excitation-contraction coupling which derives Ca ions for contractile activation from two sources: transmembrane calcium influx and calcium release from cellular stores. From the different effects on post-rest adaptation it is concluded that the individual cations influence excitation-contraction coupling more specifically and not merely by "screening-off" the negative surface charges.     

Comparison of the electromechanical responsiveness of alpha-1-adrenoceptor stimulation in ventricles of normal and cardiomyopathic hamsters

Alterations in alpha(1)-adrenoceptor (alpha(1)AR) density and related signal transduction proteins were reported in cardiomyopathic hearts in the failing stage. The electromechanical modification of alpha(1)-adrenergic stimulation in the failing heart is unclear. The present study compares the alpha(1)AR-stimulated electromechanical response in failing ventricles of genetically cardiomyopathic BIO 14.6 hamsters (280-320 days old) with that in age-matched normal Syrian hamsters. The action potential was recorded with a conventional microelectrode technique, and twitch force was measured with a transducer. In the presence of propranolol, phenylephrine increased the contraction and prolonged the action potential duration (APD) to similar values in ventricles of both strains, despite a prolonged basal APD in cardiomyopathic ventricles. The positive inotropism stimulated by phenylephrine was inhibited by staurosporine, and was potentiated by 4 beta-phorbol-12,13-dibutyrate (PDBu) in both strains. The maximum positive inotropic effect of phenylephrine in PDBu-treated ventricles of normal hamsters was significantly greater than that in BIO 14.6 hamsters. The effects of phenylephrine on the ventricular force-frequency relationship and on the mechanical restitution in both normal and BIO 14.6 strain hamsters were examined. The uniform negative force-frequency relationship and the altered mechanical restitution reveal a defect of intracellular Ca(2+) handling in cardiomyopathic BIO 14.6 hamsters. alpha(1)-Adrenergic modulation cannot convert the defective properties in the model of the failing heart. Nevertheless, phenylephrine decreased post-rest potentiation in short rest periods, and enhanced post-rest decay after longer resting periods. The results indicate that alpha(1)-adrenergic action enhances a gradual loss of Ca(2+) from the sarcoplasmic reticulum, although its action in prolonging the APD can indirectly increase the influx of Ca(2+).     

Electrical and mechanical activity of isoproterenol-damaged frog heart

The electrical and mechanical activities of myocardial strips from Rana pipiens were studied in the steady state at various stimulation frequencies and after a period of rest. The temperature of the bath was varied between + 12 and 35 degrees C. Normal myocardium was compared with that damaged by isoproterenol (ISO). The percentage change of action potential durations (APD50) and isometric force (P) was similar in ISO-damaged and control hearts at various bath temperatures with steady state stimulation rates between 20 and 100/min. At low stimulation rates (3-6/min) the prolongation of the action potential (AP) was more pronounced and the P-decrease was less in ISO-damaged myocardium compared to controls. These differences became more apparent at low bath temperatures. After 10 min of rest, APD50-90 was significantly prolonged in ISO-damaged heart and P was increased by a factor of 2 compared to controls (stimulation rate 20/min). Steady state values, on the other hand, were nearly the same in both groups. These findings are interpreted as indicating a temperature or ISO-dependent increase of electrogenic trans-sarcolemmal Ca2+-uptake during low frequency, or post-rest stimulation, either directly by an increase of the slow inward current (Isi), or indirectly by decreased K+-permeabilities.     

Cardioprotection without cardiosuppression by SEA0400, a novel inhibitor of Na+-Ca2+ exchanger, during ischemia and reperfusion in guinea-pig myocardium

The effect of SEA0400, a novel Na+-Ca2+ exchanger inhibitor, on mechanical and electrophysiological parameters of coronary-perfused guinea-pig right ventricular tissue preparation was examined during no-flow ischemia and reperfusion. Contractile force and action potential duration were decreased during no-flow ischemia, while the resting tension was increased. Upon reperfusion, transient arrhythmias were observed and contractile force returned to less than 50% of preischemic values. SEA0400 (1 microM) had no effect on the decline in contractile force during the no-flow ischemia, but abolished the rise in resting tension. SEA0400 significantly improved the recovery of contractile force after reperfusion to about 80% of the preischemic value. SEA0400 had no effect on the action potential under normal conditions and during ischemia, but significantly improved the recovery of action potential duration after reperfusion. Enhancement of the recovery of contractile force during reperfusion by SEA0400 was also observed when the drug was applied only before and during the ischemic period and when the drug was applied only during reperfusion. The present results indicate that inhibition of Na+-Ca2+ exchanger either during ischemia or during reperfusion exerts cardioprotective effects and enhances the recovery of myocardial contractile function.     

Effects of cyclopiazonic acid on triggered activities in ventricular muscle and cardiomyocytes isolated from hamster hearts

The present experiments were performed to study the actions of cyclopiazonic acid on triggered activities generated in vitro in ventricular papillary muscle and cardiomyocytes isolated from the hearts of healthy male Syrian hamsters (Biobreeders F1B). Action potentials (APs) of ventricular muscle with a diameter around 1.5 mm were recorded using a microelectrode technique and force was recorded using a transducer. Ventricular preparations were driven at 2 Hz in high [Ca]o (9 mM)-low [K]o (1 mM) solution to induce delayed after depolarizations (DADs). Triggered activities were induced on resumption of electrical stimulation after a rest period of 20 sec. Effects of cyclopiazonic acid (3-10 microM) on steady-state rhythms and post-rest triggered activities were determined. Results revealed that cyclopiazonic acid initially enhanced the amplitude of DADs and induced post-rest triggered rhythms. However, after several minutes of cyclopiazonic acid exposure, AP duration (APD) was prolonged and DADs were significantly depressed. The effects on APD and DADs were reversible after washout of cyclopiazonic acid, but the diastolic potential during rest period oscillated and was able to generate high-frequency spontaneous APs at a reduced potential level. In ventricular myocytes isolated enzymatically, ionic currents were measured using of whole-cell patch-clamp techniques. In a high [Ca]o-low [K]o solution, a series of oscillatory transient inward currents (I(ti)) were obtained on repolarization to the holding potential (-45 mV) after a depolarizing pulse to the test potential of +20 mV for 1.2 sec. Cyclopiazonic acid (10 microM) reduced significantly the magnitude of I(ti). The present results in hamster ventricular cells suggested that cyclopiazonic acid by inhibiting the sarcoplasmic reticulum (SR)-Ca2+ pump would gradually deplete the amount of Ca2+ within the SR. The consequent reduction in the amount of Ca2+ released into the cytoplasm by cyclopiazonic acid might inhibit triggered arrhythmia through a reduction of DADs and I(ti).     

Effects of adaptation to stress exposure and periodic hypoxia on bioelectric activity of cardiomyocytes of isolated heart in ischemia and reperfusion]

Action potential (AP) of cardiomyocytes was recorded in experiments on isolated perfused according to Langendorf rat hearts. The effect was estimated of preliminary adaptation to intermittent hypobaric hypoxia or to repeated short-term stress exposure on the resting potential (RP) and the amplitude and duration of action potential (APD) in global ischemia and reperfusion. It was shown that adaptation to hypoxia is more effective in prevention of ischemic fall of RP, AP and APD. In reperfusion, the parameters enumerated restored more quickly and efficiently in hearts from adapted to stress animals.     

Mechanisms and determinants of ultralong action potential duration and slow rate-dependence in cardiac myocytes

In normal cardiac myocytes, the action potential duration (APD) is several hundred milliseconds. However, experimental studies showed that under certain conditions, APD could be excessively long (or ultralong), up to several seconds. Unlike the normal APD, the ultralong APD increases sensitively with pacing cycle length even when the pacing rate is very slow, exhibiting a sensitive slow rate-dependence. In addition, these long action potentials may or may not exhibit early afterdepolarizations (EADs). Although these phenomena are well known, the underlying mechanisms and ionic determinants remain incompletely understood. In this study, computer simulations were performed with a simplified action potential model. Modifications to the L-type calcium current (I(Ca,L)) kinetics and the activation time constant of the delayed rectifier K current were used to investigate their effects on APD. We show that: 1) the ultralong APD and its sensitive slow rate-dependence are determined by the steady-state window and pedestal I(Ca,L) currents and the activation speed and the recovery of the delayed rectifier K current; 2) whether an ultralong action potential exhibits EADs or not depends on the kinetics of I(Ca,L); 3) increasing inward currents elevates the plateau voltage, which in general prolongs APD, however, this can also shorten APD when the APD is already ultralong under certain conditions; and 4) APD alternans occurs at slow pacing rates due to the sensitive slow rate-dependence and the ionic determinants are different from the ones causing APD alternans at fast heart rates.     

Dynamical effects of diffusive cell coupling on cardiac excitation and propagation: a simulation study

Cell coupling is considered to be important for cardiac action potential propagation and arrhythmogenesis. We carried out computer simulations to investigate the effects of stimulation strength and cell-to-cell coupling on action potential duration (APD) restitution, APD alternans, and stability of reentry in models of isolated cell, one-dimensional cable, and two-dimensional tissue. Phase I formulation of the Luo and Rudy action potential model was used. We found that stronger stimulation resulted in a shallower APD restitution curve and onset of APD alternans at a faster pacing rate. Reducing diffusive coupling between cells prolonged APD. Weaker diffusive currents along the direction of propagation steepened APD restitution and caused APD alternans to occur at a slower pacing rate in tissue. Diffusive current due to curvature changed APD but had little effect on APD restitution slope and onset of instability. Heterogeneous cell coupling caused APD inhomogeneities in space. Reduction in coupling strength either uniformly or randomly had little effect on the rotation period and stability of a reentry, but random cell decoupling slowed the rotation period and, thus, stabilized the reentry, preventing it from breaking up into multiple waves. Therefore, in addition to its effects on action potential conduction velocity, diffusive cell coupling also affects APD in a rate-dependent manner, causes electrophysiological heterogeneities, and thus modulates the dynamics of cardiac excitation. These effects are brought about by the modulation of ionic current activation and inactivation.     

Extracellular calcium transients and action potential configuration changes related to post-stimulatory potentiation in rabbit atrium

Extracellular calcium transients were monitored with 2 mM tetramethylmurexide at low calcium (250 microM total, 130 microM free), and action potentials were monitored together with developed tension at normal calcium (1.3 mM) during the production and decay of post-stimulatory potentiation in rabbit left atrial strips. At normal calcium, the contractile potentiation produced by a brief burst of 4 Hz stimulation is lost in three to five post-stimulatory excitations, which correlate with a negative staircase of the late action potential. At low calcium, stimulation at 4 Hz for 3-8 s results in a net extracellular calcium depletion of 5-15 microM. At the subsequent potentiated contraction (1-45 s rest), total extracellular calcium increases by 4-8 microM. The contractile response at a second excitation is greatly suppressed and results in little or no further calcium shift; the sequence can be repeated immediately thereafter. Reducing external sodium to 60 mM (sucrose replacement) enhances post-rest contractions, suppresses the late action potential, nearly eliminates loss of contractility and net calcium efflux at post-rest excitations, and markedly reduces extracellular calcium depletion during rapid stimulation. 4-Aminopyridine (1 mM) markedly suppresses the rapid early repolarization of this preparation at post-rest excitations and the loss of contractility at post-rest stimulation from the rested state; during a post-stimulatory potentiation sequence at low calcium, replenishment of extracellular calcium takes several post-stimulatory excitations. Ryanodine (10 nM to 5 microM) abolishes the post-stimulatory contraction at rest periods of greater than 5 s. If the initial repolarization is rapid, ryanodine suppresses the late action potential, calcium efflux during quiescence is greatly accelerated, and subsequent excitations do not result in an accumulation of extracellular calcium. A positive staircase of the early action potential correlates with the magnitude of net extracellular calcium depletion. These findings demonstrate that negative contractile staircases at post-rest stimulation correspond closely to an accumulation of extracellular calcium at activation and a negative staircase of the late action potential; the correlation of these three events suggests that electrogenic sodium-calcium exchange is the common underlying mechanism.     

α—人心房钠尿因子对离体豚鼠心肌收缩力和动作电位...

The effect of alpha-hANF on contractile force and action potential duration (APD) of isolated myocardium in guinea pig was investigated. At the level of 20 nmol/L and 40 nmol/L alpha-hANF, the contraction amplitude and rate of contraction phase decreased to a remarkable extent. And at 40 nmol/L, APDs were shortened significantly 20 min after alpha-hANF. The results suggest that there exists a direct inhibitory effect of alpha-hANF on myocardial contractile force and action potential duration.     

Study of the restitution of action potential duration using the artificial neural network

It is widely accepted that the APD (action potential duration) restitution plays a key role in the initializing and maintaining of the reentry arrhythmias. The Luo-Rudy II models paced with different protocols showed that the current APD had a complex relation with the previous APDs and diastole intervals (DIs). This relation could not be accurately described by a single exponential function. We used an artificial neural network to formularize this relation. The results suggested that back-propagation (BP) network could predict the current APD from the information of the first three previous beats. This would help provide a target for potential anti-arrhythmic therapies.     

Nonlinear dynamics of two-dimensional cardiac action potential duration mapping model with memory

The aim of this work is the analysis of the nonlinear dynamics of two-dimensional mapping model of cardiac action potential duration (2D-map APD) with memory derived from one dimensional map (1D-map). Action potential duration (APD) restitution, which relates APD to the preceding diastolic interval (DI), is a useful tool for predicting cardiac arrhythmias. For a constant rate of stimulation the short action potential during alternans is followed by a longer DI and inversely. It has been suggested that these differences in DI are responsible for the occurrence and maintenance of APD alternans. We focus our attention on the observed bifurcations produced by a change in the stimulation period and a fixed value of a particular parameter in the model. This parameter provides new information about the dynamics of the APD with memory, such as the occurrence of bistabilities not previously described in the literature, as well as the fact that synchronization rhythms occur in different ways and in a new fashion as the stimulation frequency increases. Moreover, we show that this model is flexible enough as to accurately reflect the chaotic dynamics properties of the APD: we have highlighted the fractal structure of the strange attractor of the 2D-map APD, and we have characterized chaos by tools such as the calculation of the Lyapunov exponents, the fractal dimension and the Kolmogorov entropy, with the next objective of refining the study of the nonlinear dynamics of the duration of the action potential and to apply methods of controlling chaos.

     

The effects of acetylcholine and catecholamines on post-rest phenomena in rabbit and guinea-pig atria and on accompanying shifts of 45Ca in guinea-pig atrial muscle

We studied the pattern of post-rest activation and shifts of 45Ca in the isolated mammalian atrial muscle. The first contraction evoked in the rabbit and guinea-pig atrial muscle after 10 min rest was several times stronger than the steady-state beats at a rate of 60/min. Contractile force (CF) declined to 20-50% of control during the next 1-3 beats and recovered to the pre-rest level upon subsequent stimulation. The post-rest beats were negligibly affected by noradrenaline (NA), isoproterenol (IS) acetylcholine (ACh), carbachol (CCh) and Ni, whereas the steady-state beats were readily affected by all these drugs or ions. Post-rest potentiation was completely inhibited by caffeine in a concentration of 10 mM. The guinea-pig atria, equilibrated for 60 min in 45Ca containing solution and stimulated at a rate of 60/min, contained 4.47 +/- 0.16 mmol 45Ca/kg wet weight (w.w.). Ten min of rest resulted in a drop of this content to 3.52 +/- 0.13 mmol/kg w.w. despite the continued presence of 45Ca in the superfusing solution. Three initial post-rest beats resulted in further drop of the content of 45Ca to 2.62 +/- 0.14 mmol/kg w.w. Continued post-rest stimulation resulted in a recovery of the pre-rest 45Ca content. This recovery was inhibited by ACh and CCh. Both drugs inhibited 45Ca loss during the initial 3 beats. Neither this loss nor recovery were affected by IS. It is concluded that calcium (Ca) fraction described in the previous papers [11, 15] as Ca2 in the guinea-pig ventricular muscle plays an important role in the force-frequency relations also in the atrial muscle. However, unlike in ventricular muscle only about half of it is released from the cells upon rest whereas the remaining Ca is taken up by the release compartment and used to activate the strong post-rest contraction. It is thereafter extruded from the cells which results in severe depletion of intracellular Ca stores. Fraction Ca2 is re-accumulated during the post-rest stimulation resulting in recovery of the contractile force.     

Focal extracellular potential: a means to monitor electrical activity in single cardiac myocytes

The focal extracellular potential (FEP) described in this study is an electrophysiological signal related to the transmembrane potential (V(m)) of cardiac myocytes that avoids the mechanical fragility, interference with contraction, and intracellular contact associated with conventional whole cell recording. One end of a frog ventricular myocyte was secured into a glass holding pipette. The FEP was measured differentially between this pipette and a bath pipette while the cell was voltage- or current-clamped by a third whole cell pipette. The FEP appeared as an amplitude-truncated action potential, while FEP duration accurately reflected the action potential duration (APD) at 90% repolarization (APD(90)). FEP magnitude increased as the holding pipette K(+) concentration ([K(+)]) was increased. The FEP-voltage relation was quasi-linear at negative V(m) with a slope that increased with elevated holding pipette [K(+)]. Increasing the membrane conductance inside the holding pipette by adding amphotericin B or cromakalim linearized the FEP-voltage relation across all V(m). The FEP accurately reported electrical activation and APD(90) during changes of stimulation frequency and episodes of cellular stretch.     

Dynamics of human atrial cell models: restitution, memory, and intracellular calcium dynamics in single cells

Mathematical models of cardiac cells have become important tools for investigating the electrophysiological properties and behavior of the heart. As the number of published models increases, it becomes more difficult to choose a model appropriate for the conditions to be studied, especially when multiple models describing the species and region of the heart of interest are available. In this paper, we will review and compare two detailed ionic models of human atrial myocytes, the Nygren et al. model (NM) and the Courtemanche et al. model (CM). Although both models include the same transmembrane currents and are largely based on the same experimental data from human atrial cells, the two models exhibit vastly different properties, especially in their dynamical behavior, including restitution and memory effects. The CM produces pronounced rate adaptation of action potential duration (APD) with limited memory effects, while the NM exhibits strong rate dependence of resting membrane potential (RMP), limited APD restitution, and stronger memory, as well as delayed afterdepolarizations and auto-oscillatory behavior upon cessation of rapid pacing. Channel conductance modifications based on experimentally measured changes during atrial fibrillation modify rate adaptation and memory in both models, but do not change the primary rate-dependent properties of APD and RMP for the CM and NM, respectively. Two sets of proposed changes to the NM that yield a spike-and-dome action potential morphology qualitatively similar to the CM at slow pacing rates similarly do not change the underlying dynamics of the model. Moreover, interchanging the formulations of all transmembrane currents between the two models while leaving calcium handling and ionic concentrations intact indicates that the currents strongly influence memory and the rate adaptation of RMP, while intracellular calcium dynamics primarily determine APD rate adaptation. Our results suggest that differences in intracellular calcium handling between the two human atrial myocyte models are responsible for marked dynamical differences and may prevent reconciliation between the models by straightforward channel conductance modifications.     

Frequency-dependent effects of various IKr blockers on cardiac action potential duration in a human atrial model

Rapidly activating K(+) current (I(Kr)) blockers prolong action potential (AP) duration (APD) in a reverse-frequency-dependent manner and may induce arrhythmias, including torsade de pointes in the ventricle. The I(Kr) blocker dofetilide has been approved for treatment of atrial arrhythmias, including fibrillation. There are, however, a limited number of studies on the action of I(Kr) blockers on atrial AP. When we tested a mathematical model of the human atrial AP (M Courtemanche, RJ Ramirez, S Nattel. Am J Physiol Heart Circ Physiol 275: H301-H321, 1998) to examine the effects of dofetilide-type I(Kr) blockade, this model could not reproduce the reverse-frequency-dependent nature of I(Kr) blockade on atrial APD. We modified the model by introducing a slowly activating K(+) current activation parameter. As the slow time constant was increased, dofetilide-type blockade induced more prominent reverse-frequency-dependent APD prolongation. Using the modified model, we also examined the effects of two more types of I(Kr) blockade similar to those of quinidine and vesnarinone. Voltage- and time-dependent block of I(Kr) through the onset of inhibition by quinidine is much faster than by vesnarinone. When we incorporated the kinetics of the effects of these drugs on I(Kr) into the model, we found that quinidine-type blockade caused a reverse-frequency-dependent prolongation of APD that was similar to the effect of dofetilide-type blockade, whereas vesnarinone-type blockade did not. This finding coincides with experimental observations. The lack of the reverse frequency dependence in vesnarinone-type blockade was accounted for by the slow development of I(Kr) blockade at depolarized potentials. These results suggest that the voltage- and time-dependent nature of I(Kr) blockade by drugs may be critical for the phenotype of the drug effect on atrial AP.     

Mechanisms underlying adaptation of action potential duration by pacing rate in rat myocytes

Heart rate is an essential determinant of cardiac performance. In rat ventricular myocytes, a sudden increase in rate yields to a prolongation of the action potential duration (APD). The mechanism underlying this prolongation is controversial: it has been proposed that the longer APD is due to either: (1) a decrease in K⁺ currents only or (2) an increase in Ca²⁺ current only. The aim of this study was to quantitatively investigate the contribution of Ca²⁺ and K⁺ currents in the adaptation of APD to pacing rate. Simulation using a mathematical model of ventricular rat cardiac cell model [Pandit, S.V., Clark, R.B., Giles, W.R., Demir, S.S., 2001. A mathematical model of action potential heterogeneity in adult rat left ventricular myocytes. Biophys. J. 81, 3029–3051] predicted a role in the prolongation of APD for K⁺ currents only. In patch clamp experiments, increasing the pacing rate leads to a significant increase in APD in both control and detubulated myocytes, although it was more marked in control than detubulated myocytes. Supporting the model prediction, we observed that increasing stimulation frequency leads to a decrease in K⁺ currents in voltage clamped rat ventricular myocytes (square and action potential waveforms), and to a similar extent in both cell types. We have also observed that frequency-dependent facilitation of Ca²⁺ current occurred in control cells but not in detubulated cells (square and action potential waveforms). From these experiments, we calculated that the relative contribution of Ca²⁺ and K⁺ currents to the longer APD following an increase in pacing rate is 65% and 35%, respectively. Therefore, in contrast to the model prediction, Ca²⁺ current has a significant role in the adaptation of APD to pacing rate. Finally, we have introduced a simplistic modification to the Pandit's model to account for the frequency-dependent facilitation of Ca²⁺ current.     

Cardiac mechano-electric feedback and electrical restitution in humans

Electrical restitution in the heart is the property whereby the action potential duration and conduction velocity of a beat of altered cycle length vary according to its immediacy to the preceding basic beat--the coupling interval, usually the diastolic interval. In general, action potential duration (APD) increases with increasing coupling interval, and the relation between action potential duration and the preceding diastolic interval describes the APD restitution curve. The latter has recently been the focus of considerable interest since the steepness of the initial part of the restitution curve plays an important role in electrical stability and arrhythmogenesis. Mechanical stretch has been shown to alter APD and hence refractoriness either through stretch activated channels or by influencing calcium cycling. Such an effect on refractoriness has been proposed as a mechanism of arrhythmogenesis particularly if spatially inhomogeneities manifest within the heart. Here, we review (1) the spatial and temporal characteristics of APD restitution in humans; (2) previously reported work showing that mechanical loading differentially effects APD of interpolated beats of altered cycle length, and hence alters the slope of the APD restitution curve; and (3) evidence that inhomogeneity of APD restitution slope may be an important factor in arrhythmogenesis.     

The action of ultrasound on the contraction strength and action potential of the papillary muscle of the rat heart

In experiments on isolated rat papillary muscles the effects of therapeutic doses of ultrasound (US) (intensity, less than 2 W/cm2) with frequency of 0.88 MHz on contraction force and action potential (AP) were studied. 12 muscles (from 14) responded to 3-min exposition of the US with a rise both in contraction force and in resting tension. Sensitivity to US and a value of inotropic effect changed significantly between the preparation, and the threshold intensities of US varied from 0.3 to 2 W/cm2. In 3 experiments the inotropic effect of US was more than 100%, but in others it was about 50%. Two preparations were not sensitive to the US. The positive inotropic effect of US was accompanied by membrane depolarization (up to 20 mV) and by prolongation of AP duration measured at 10% of its amplitude (APD10). The correlation between the increase in contraction force and APD10 was demonstrated. Some preparations responded to US with high depolarization (up to 50 mV) and were inexcitable. The US induced an increase in temperature less than 1 degree C, therefore all the effects of US could not be explained as a result of temperature rise.     

乙酰胆碱对豚鼠心房肌和心室肌的动作电位和收缩力的不同作用

实验采用标准玻璃微电极细胞内记录技术记录心肌细胞动作电位（action potential,AP）、肌力换能器记录心肌收缩力（force contraction,Fc）,研究乙酰胆碱（acetylcholine,ACh）对离体豚鼠心房肌、心室肌的作用。结果表明,10μmol/L ACh可缩短心房肌、心室肌动作电位的时程（action potential duration,APD）。心房肌APD在给药前后分别为208.57±36.05ms及101.78±14.41ms（n=6,P<0.01）,心室肌APD在给药前后分别为286.73±36.11ms及265.16±30.06 ms（n=6,P<0.01）。心房肌动作电位的幅度（action potential amplitude,APA）也降低,给药前后分别为88.00±9.35 mV及62.62±20.50 mV（n=6,P<0.01）,而心室肌APA无明显变化。ACh还降低心房肌、心室肌的收缩力,心房肌、心室肌Fc的抑制率分别为100％（n=6,P<0.01）和37.57±2.58％（n=6,P<0.01）。ACh对心房肌、心室肌APD和Fc的抑制作用在一定范围内（1nmol/L～100μmol/L）随ACh浓度的增高而增强。用Scott法求出ACh对心房肌、心室肌APD缩短作用的KD值,分别为0.275和0.575μmol/L,对Fc抑制作用的KD值分别为0.135和0.676μmol/L。各浓度下ACh对心房肌效应与心室肌效应作组间t检验,从10nmol/L到0.1mmol/L均有显著的统计学差异。此外,10μmol/L阿托品及20mmol/L