Reverse excitation-contraction coupling: Ca2+ ions as initiators of arrhythmias.
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Animals↗
Biomedical subjects
H E ter Keurs
Publications and source records attributed to H E ter Keurs.
A 2D finite element model of the interventricular septum under normal and abnormal loading.
The interventricular septum is the structure that separates the left and right ventricles of the heart. Under normal loading conditions, it is concave to the left ventricle, but under abnormal loading the septum flattens and occasionally inverts. In the past, the septum has frequently been modelled as integral to the left ventricle with the effects of pressure from the right ventricle being ignored. Under abnormal loading, the septum has been described as behaving equivalent to a "flapping sail". There has been no consideration of structural behaviour under these conditions. A 2-D plane stress FE model of the septum was used to investigate the difference in structural behaviour of the septum during diastole between normal and abnormal loading. The biaxial stress patterns that develop are distinctively disparate. Under normal loading, the septum behaves much like a thick-walled cylinder subject to internal and external pressure, with the resulting stresses being circumferential tension and radial compression, both varying with radius. These stresses are very low throughout most of diastole. However, under abnormal loading, the septum behaves in an arch-like fashion, with high compressive stresses almost circumferential in direction, combined with radial compression. We conclude that right ventricular pressures cause bending effects in the wall of the heart, and that under abnormal loading, the compressive stresses that develop in the septum may lead to an understanding of certain, previously unexplained, pathological conditions.
Compressive Strength↗
Stretch and quick release of rat cardiac trabeculae accelerates Ca2+ waves and triggered propagated contractions.
Rapid shortening of active cardiac muscle [quick release (QR)] dissociates Ca2+ from myofilaments. We studied, using muscle stretches and QR, whether Ca2+ dissociation affects triggered propagated contractions (TPCs) and Ca2+ waves. The intracellular Ca2+ concentration was measured by a SIT camera in right ventricular trabeculae dissected from rat hearts loaded with fura 2 salt, force was measured by a silicon strain gauge, and sarcomere length was measured by laser diffraction while a servomotor controlled muscle length. TPCs (n = 27) were induced at 28 degrees C by stimulus trains (7.5 s at 2.65 +/- 0.13 Hz) at an extracellular Ca2+ concentration ([Ca2+]o) = 2.0 mM or with 10 microM Gd3+ at [Ca2+]o = 5.2 +/- 0.73 mM. QR during twitch relaxation after a 10% stretch for 100-200 ms reduced both the time between the last stimulus and the peak TPC (PeakTPC) and the time between the last stimulus and peak Ca2+ wave (PeakCW) and increased PeakTPC and PeakCW (n = 13) as well as the propagation velocity (Vprop; n = 8). Active force during stretch also increased Vprop (r = 0.84, n = 12, P < 0.01), but Gd3+ had no effect (n = 5). These results suggest that Ca2+ dissociation by QR during relaxation accelerates the initiation and propagation of Ca2+ waves.
Actin Cytoskeleton↗
Effect of transient stretch on intracellular Ca2+ during triggered propagated contractions in intact trabeculae.
Transient stretch of cardiac muscle during a twitch contraction may dissociate Ca2+ from myofilaments into the cytosol at the moment of quick release of the muscle. We studied the effect of stretch and quick release of trabeculae on changes in intracellular Ca2+ ([Ca2+]i) during triggered propagated contractions (TPCs). Trabeculae were dissected from the right ventricle of 9 rat hearts. [Ca2+]i was measured using electrophoretically injected fura-2. Force was measured using a silicon strain gauge and sarcomere length was measured using laser diffraction techniques. Reproducible TPCs (n = 13) were induced by trains of electrical stimuli (378 +/- 19 ms interval) for 7.5 s at [Ca2+]o of 2.0 mM (27.9 +/- 0.2 degrees C). The latency of the TPC force and the underlying increase in [Ca2+]i was calculated from the time (TimeF) between the last stimulus and the peak of TPC force (PeakF), or the time (TimeCa) between the last stimulus and the peak of the increase in [Ca2+]i during the TPCs (PeakCa). As a result of a 10% increase in muscle length for 150-200 ms during the last stimulated twitches, TimeF and TimeCa decreased and PeakF and PeakCa increased significantly (n = 13). In addition, transient stretch sometimes induced a twitch contraction subsequent to the accelerated TPC and its underlying increase in [Ca2+]i. These results suggest that Ca2+ binding and dissociation from the myofilaments by the stretch and quick release of muscle may modulate the TPC force and the underlying increases in [Ca2+]i and play an important role in the induction of arrhythmias.
Actin Cytoskeleton↗
Damage induced arrhythmias: mechanisms and implications.
Little is known about the role played by non-uniform myocardial stress and strain distributions and by non-uniform excitation contraction coupling in mechanisms underlying the premature beats that initiate an arrhythmia. We will review the evidence in support of a mechanism in which both non-uniform contraction and increased Ca2+ load of cells adjacent to acutely damaged cells are essential in the "spontaneous" generation of Ca2+ transients during the relaxation phase of the electrically driven twitch. The putative mechanism of initiation of the propagating Ca2+ waves involves feedback of rapid length (or force) changes to dissociation of Ca2+ from the contractile filaments. A novel aspect of this concept is that these mechanically elicited Ca2+ transients induce propagating Ca2+ waves that travel into the adjacent normal myocardium and cause after-depolarizations, which, in turn, may cause premature action potentials. These premature action potentials will further load the cells with Ca2+, which promotes the subsequent generation of propagating Ca2+ transients and leads to triggered arrhythmias. The damage-induced premature beats may also initiate re-entry arrhythmias in non-uniform myocardium. These observations strongly support the concept that abnormal cellular Ca2+ transport plays a crucial role in the initiation of arrhythmias in damaged and non-uniform myocardium.
Animals↗
Calcium waves: physiological relevance in cardiac function.
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Animals↗
Ca(2+)-dependence of passive properties of cardiac sarcomeres.
Rat cardiac trabeculae constitute a well-known experimental model in studies of cardiac contraction at the sarcomere level. Continuous measurement of length of the sarcomeres (SL) by laser diffraction technique permits one to monitor the active shortening of the contractile units during generation of force. When the preparation is stimulated repetitively (0.5 Hz) by electrical pulses, active shortenings are separated by periods corresponding approximately to the diastolic interval in the heart and wherein normally no major contractile event would have been expected. In contrast to this expectation, studies conducted with high-resolution (2-4 nm) SL measurements technique revealed that sarcomeres continuously lengthened (by 10-60 nm) from the end of twitch relaxation to the next stimulation. Such lengthening resulted from an internal expansion of the sarcomere and not from stretch exerted by extra-sarcomeric sources. We further characterized diastolic changes by measuring sarcomere stiffness (Sarc-Stiff) estimated from the response to short bursts (30 ms) of sinusoidal perturbations (frequency: 500 Hz) at 5 moments of the resting interval separating twitches. Sarc-Stiff increased continuously by approximately 30% during the diastolic interval (29 degrees C, pH: 7.4, [Ca2+]o = 1 mM). We then investigated during the same period the intracellular dynamics of Ca2+, as a major determinant of sarcomere motions in muscle. Intracellular free-Ca2+ concentration ([Ca2+]i) was measured continuously in trabeculae microinjected with the fluorescent Ca(2+)-probe Fura-2 and stimulated at 0.5 Hz. It appeared that the Ca(2+)-transient, which drives the twitch, did not end with the apparent relaxation of the force. Instead, [Ca2+]i kept decreasing in an exponential manner throughout the diastolic interval. At [Ca2+]o = 1 mM, [Ca2+]i decreased from 230 to 90 nM with a time constant of approximately 250 ms. The similarity in time courses of Ca(2+)-decline and of Sarc-Stiff increase suggested that properties of resting sarcomeres were related to [Ca2+]i in the sub-micromolar range. In order to examine this possibility, Sarc-Stiff was measured in chemically skinned trabeculae, i.e. in a preparation allowing control of [Ca2+] surrounding the sarcomeres. Sarc-Stiff was measured at different [Ca2+] from 1 to 450 nM. We found that 1) below 70 nM, Sarc-Stiff was independent on [Ca2+], 2) between 70 and 200 nM, i.e., approximately the range wherein [Ca2+]i decreased during diastole in intact muscle, Sarc-Stiff decreased by approximately 50% with increase of [Ca2+] and 3) above 200 nM, Sarc-Stiff increased steeply with increase of [Ca2+] as was expected from Ca(2+)-dependent attachment of cross-bridges between actin and myosin. The data fitted accurately to the sum of 2 sigmoid functions: 1) at [Ca2+] < 200 nM, Sarc-Stiff decreased with increase of [Ca2+] with a Hill coefficient (nH) = -2.6 and [Ca2+] at half maximal activation (EC50) = 0.16 +/- 0.013 microM; 2) at [Ca2+] > 200 nM, Sarc-Stiff increased with [Ca2+] (nH: 2.1; EC50:3.4 +/- 0.3 microM) consistent with Ca(2+)-dependent attachment of cross-bridges. It was possible to reproduce the diastolic variation of Sarc-Stiff observed in intact muscle by using the time course of [Ca2+]i in the Sarc-Stiff--[Ca2+] relationship determined from skinned trabeculae. We conclude that physical properties of the sarcomeres are inversely related to Ca2+ below 200 nM, i.e., in a range of concentrations where the myocytes operate during diastole while the influence of cross-bridges is negligible.
Animals↗
Ca2+ waves during triggered propagated contractions in intact trabeculae. Determinants of the velocity of propagation.
During triggered propagated contractions, Ca2+ waves travel along cardiac trabeculae with a constant velocity (Vprop) ranging from 0. 34 to 5.47 mm/s. To explore the determinants of Vprop, we studied (1) the relationship between [Ca2+]i and Vprop and (2) the effect of low concentrations of caffeine on Vprop. Trabeculae were dissected from the right ventricle of rat hearts. [Ca2+]i was measured using electrophoretically injected fura-2 and an image-intensified CCD camera. Force was measured using a silicon strain gauge, and sarcomere length was measured using laser diffraction techniques. After induction of reproducible Ca2+ waves by trains of electrical stimuli (2.5 Hz) at 21.9+/-0.2 degrees C, the number of stimuli or [Ca2+]o was varied in 9 trabeculae. In 5 trabeculae, the effects of caffeine (0.1 to 1.0 mmol/L) at [Ca2+]o of 2.2+/-0.3 mmol/L were determined. All images were recorded under stable conditions of wave propagation. The increment in [Ca2+]i during the last electrically stimulated transient (DeltaCaT) and [Ca2+]i just before onset of the Ca2+ waves (CaD) were used to estimate the Ca2+ loading of the sarcoplasmic reticulum (SR) and the myoplasm, respectively. The ratio (DeltaCaW/DeltaCaT) of the [Ca2+]i increment during the waves (DeltaCaW) to DeltaCaT was used to estimate the probability of opening of the SR-Ca2+ release channel during wave propagation. As a result of an increase of the number of stimuli or [Ca2+]o, Vprop increased in proportion to (1) DeltaCaT (r=0.82); (2) CaD (r=0.88); (3) DeltaCaW (r=0.85); and (4) DeltaCaW/DeltaCaT (r=0.74). The addition of caffeine (</=0.3 mmol/L) increased Vprop for any DeltaCaT and any DeltaCaW, revealing an increased sensitivity of Vprop to DeltaCaT and DeltaCaW. In contrast, caffeine had little effect on the relationship between Vprop and CaD and no effect on that between Vprop and DeltaCaW/DeltaCaT. These results suggest that both the cellular Ca2+ loading and open probability of the SR-Ca2+ release channels determine the velocity of propagation of Ca2+ waves.
Animals↗
Microtubules in cardiac hypertrophy: a mechanical role in decompensation?
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Animals↗
Damage-induced arrhythmias: reversal of excitation-contraction coupling.
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Action Potentials↗
Modelling the mechanical properties of cardiac muscle.
A model of passive and active cardiac muscle mechanics is presented, suitable for use in continuum mechanics models of the whole heart. The model is based on an extensive review of experimental data from a variety of preparations (intact trabeculae, skinned fibres and myofibrils) and species (mainly rat and ferret) at temperatures from 20 to 27 degrees C. Experimental tests include isometric tension development, isotonic loading, quick-release/restretch, length step and sinusoidal perturbations. We show that all of these experiments can be interpreted with a four state variable model which includes (i) the passive elasticity of myocardial tissue, (ii) the rapid binding of Ca2+ to troponin C and its slower tension-dependent release, (iii) the kinetics of tropomyosin movement and availability of crossbridge binding sites and the length dependence of this process and (iv) the kinetics of crossbridge tension development under perturbations of myofilament length.
Actin Cytoskeleton↗
Ca(2+)-dependence of diastolic properties of cardiac sarcomeres: involvement of titin.
The stiffness of the sarcomeres was studied during the diastolic interval of 18 stimulated (0.5 Hz) cardiac trabeculae of rat (pH 7.4; temperature = 25 degrees C). Sarcomere length (SL) and force (F) were measured using, respectively, laser diffraction techniques (resolution: 4 nm) and a silicon strain gauge (resolution: 0.63 microN). Sinusoidal perturbations (frequency = 500 Hz) were imposed to the length of the preparation. The stiffness was evaluated from the corresponding F and SL sinusoids by analysis of both signals together either in the time domain or in the frequency domain. A short burst (duration = 30 ms) of sinusoidal perturbations was repeated at 5 predetermined times during diastole providing 5 measurements of stiffness during the time interval separating two twitches. These measurements revealed that stiffness increases by approximately 30% during diastole, while a simultaneous expansion of the sarcomeres (amplitude = 10-60 nm) was detected. Measurements of the fluorescence of fura-2 under the same conditions revealed a continuous exponential decline of [Ca2+]i from 210 to 90 nM (constant of time approximately 300 ms) during diastole. In order to test the possibility that the increase of sarcomere stiffness and the decline of [Ca2+]i were coupled during diastole of intact trabeculae, we studied the effect of different free Ca(2+)-concentrations ([Ca2+]) between 1 and 430 nM on sarcomere stiffness in rat cardiac trabeculae skinned by saponin (n = 17). Stiffness was studied using 500 Hz sinusoidal perturbations of muscle length (ML). We found that, below 70 nM, the stiffness was independent of [Ca2+]; between 70 and 200 nM, the stiffness declined with increase of [Ca2+]; above 200 nM, the stiffness increased steeply with [Ca2+]. The data fitted accurately to the sum of two sigmoids (Hill functions): (1) at [Ca2+] < 200 nM the stiffness decreased with [Ca2+] (EC50 = 160 +/- 13 nM; n = -2.6 +/- 0.7) and (2) at [Ca2+] > 200 nM, stiffness increased with [Ca2+] (EC50 = 3.4 +/- 0.3 microM; n = 2.1 +/- 0.2) due to attachment of cross-bridges. From these results, it was possible to reproduce accurately the time course of diastolic stiffness observed in intact trabeculae and to predict the effect on stiffness of a spontaneous elevation of the diastolic [Ca2+]. Identical stiffness measurements were performed in 4 skinned preparations exposed to a cloned fragment of titin (Ti I-II) which has been shown to exhibit a strong interaction with F-actin in vitro. It was anticipated that Ti I-II would compete with endogenous titin for the same binding site on actin in the I-band. Below 200 nM, Ti I-II (2 microM) eliminated the Ca(2+)-dependence of stiffness. These results are consistent with the hypothesis that the Ca(2+)-sensitivity of the sarcomeres at [Ca2+] < 200 nM, i.e. where the myocytes in intact muscle operate during diastole, involves an association between titin molecules and the thin filament.
Animals↗
Effect of misoprostol on myocardial contractility in rats treated with cyclosporin A.
The nephrotoxic side effects of the immunosuppressant cyclosporin A in animals and humans are well known. Misoprostol, a prostaglandin E analog, is used clinically in organ-transplant recipients taking cyclosporin A to protect against these side effects. We reported previously that long-term treatment of rats with cyclosporin A causes a diminution in myocardial peak contractile stress. There is an associated spontaneous sarcomere activity and rest depression of force in the absence of a change in myofilaments sensitivity to intracellular Ca2+. Here we investigated the potential protective effects of misoprostol on the myocardium of cyclosporin A-treated rats. Rats were treated with either cyclosporin A, misoprostol, or their combination. Force-[Ca2+]o and -[Sr2+]o, and force-interval relations as well as the sarcomere length were studied in trabeculae isolated from the right ventricles. At suboptimal [Ca2+]o, cyclosporin A shifted the force-[Ca2+]o relation to the left but reduced peak contractile stress by approximately 35% at the highest (optimal) [Ca2+]o. Co-treatment with misoprostol prevented the leftward shift, and treatment with misoprostol alone did not cause a leftward shift. The diminution of peak stress, however, did not recover with misoprostol treatment, and stress was further reduced. Treatment with only misoprostol also reduced stress generated by the muscles more than that by cyclosporin A alone. Intriguingly, activation of the myofilaments by Sr2+ failed to recover peak stress to control levels in any group treated with misoprostol. Unlike cyclosporin A, however, rest potentiation of force was more pronounced, and spontaneous sarcomere activity was absent with misoprostol. No histopathologic changes were observed with cyclosporin A or misoprostol treatment. Misoprostol modifies the cyclosporin A-induced changes in the Ca2+ handling, but further decreases the stress generated by the muscles.
Animals↗
Ca2+ waves during triggered propagated contractions in intact trabeculae.
Triggered propagated contractions (TPCs) starting from damaged regions travel along multicellular cardiac muscle preparations. We have reported that octanol (100 microM) inhibits TPCs. The inhibitory effect of octanol on propagation of TPCs could be due to an effect of octanol on Ca(2+)-induced Ca2+ release (CICR) mediated by Ca2+ diffusion inside the single cell or on the diffusion of Ca2+ from cell to cell via gap junctions (GJs). Therefore, we studied the regional changes in intracellular Ca2+ concentration ([Ca2+]i) during TPCs and the effect of octanol on the permeability of gap junctions (PGJ) in rat cardiac trabeculae. [Ca2+]i was measured using electrophoretically injected fura 2 and an image-intensified charge-coupled device camera. PGJ was calculated from the diffusion coefficient for fura 2 in trabeculae (Dtrab) and in the myoplasm (Dmyop). After 1- and 3-h superfusion with 100 microM 1-octanol, Dmyop showed no significant changes, whereas Dtrab was reduced significantly. Therefore, calculated PGJ was reduced from 4.15 x 10(-5) to 2.10 x 10(-5) and 0.86 x 10(-5) cm/s, respectively. The propagation velocity of the regional increases in [Ca2+]i during TPCs was constant, averaging 1.69 +/- 1.48 mm/s (range 0.34-5.47 mm/s, n = 10). These observations support the hypothesis that TPCs are initiated near the damaged ends of trabeculae and are propagated by CICR from the sarcoplasmic reticulum mediated by diffusion of Ca2+ through cells and from cell to cell through GJs.
1-Octanol↗
Dynamics of viscoelastic properties of rat cardiac sarcomeres during the diastolic interval: involvement of Ca2+.
1. Cardiac sarcomere stiffness was investigated during diastole in eighteen trabeculae dissected from the right ventricle of rat heart. The trabeculae were stimulated at 0.5 Hz, in a modified Krebs-Henseleit solution (pH, 7.4; 25 degrees C). Sarcomere length (SL) was measured using high resolution (+/-2 nm) laser diffraction techniques. Force (F) was measured with a silicon strain gauge. 2. SL increased exponentially (amplitude, 25 +/- 9 nm; n = 15) throughout diastole. This increase occurred even at slack SL, showing that this phenomenon was due to an internal expansion. The majority of the muscles showed discrete spontaneous fluctuations of SL (amplitude < 20 nm) starting approximately 1 s after the end of the twitch. 3. The intracellular free Ca2+ concentration ([Ca2+]i) was measured from the fluorescence of microinjected fura-2 salt in seven trabeculae under the same experimental conditions. [Ca2+]i continuously declined (from 240 to 90 nM) during diastole following a monoexponential time course (time constant, 210-325 ms). 4. The stiffness of the sarcomere was evaluated at 10, 30, 50, 70 and 90% of diastole using bursts (30 ms) of 500 Hz sinusoidal perturbations of muscle length (amplitude of SL oscillations < 30 nm). At 1 nM external Ca2+ concentration ([Ca2+]o), the average stiffness modulus (Mod) increased from 9.3 +/- 0.6 to 12 +/- 0.6 nN mm-2 micron-1 (n = 18; P < 0.05), while the average phase shift (phi) between F and SL signals decreased from 84 +/- 3 to 73 +/- 4 deg (n = 18; P < 0.05) between 10 and 90% during diastole. The increase in Mod and the decrease in phi reversed when spontaneous activity occurred. When [Ca2+]o was raised to 2 mM, the stiffness time course reversed approximately 450 ms earlier, simultaneously with the occurrence of spontaneous activity. 5. Our results show that diastole is only an apparent steady state and suggest that the structural system responsible for the viscoelastic properties of the sarcomere is regulated by [Ca2+]i in the submicromolar range. Different possible origins of the dynamic changes in viscoelasticity during diastole are discussed.
Animals↗
Diastolic viscoelastic properties of rat cardiac muscle; involvement of Ca2+.
Diastolic cardiac sarcomere stiffness, sarcomere length changes, and calcium concentration [Ca2+]i were investigated in 18 trabeculae, dissected from the right ventricle of rat heart. [Ca2+]i declined following a mono-exponential diastolic time course with a time constant of 210-350 ms. During diastole, ([Ca2+]o = 1 mM); sarcomere length (SL) increases (amplitude: 5-65 nm; time constant: 600 ms). Eighty percent of muscles showed discrete spontaneous motion of sarcomeres near the end of diastole; this phenomenon occurred earlier at higher [Ca2+]o. The stiffness modulus of the sarcomere (MOD) increased by 30% during diastole (n = 158; p < 0.05), while the phase difference, phi, between force and SL decreased by 13% (n = 158; p < 0.05). The increase of MOD and the decrease of phi reversed when spontaneous activation occurred. These results show that the mechanical diastolic properties of the cardiac sarcomere are time dependent. The time dependence of the diastolic properties can be faithfully reproduced by a simple linear four element viscoelastic model. The diastolic changes of MOD and of phi could be reproduced by assuming an exponential change of the elastic and viscous coefficients of the model over time with a time constant similar to the time constant of change of [Ca2+]i. We suggest that the simplest combination of structural counterparts of the model in the sarcomere consists of titin bound to both actin and myosin in the myofibril, while the sarcomere is in parallel with another purely elastic element. We propose that the Ca(2+)-dependence of diastolic stiffness might be the result of an inverse relation between [Ca2+]i and the affinity of titin for actin.
Animals↗
Ca2+ 'sparks' and waves in intact ventricular muscle resolved by confocal imaging.
The [Ca2+]i transient in heart is now thought to involve the recruitment and summation of discrete and independent "units" of Ca2+ release (Ca2+ "sparks") from the sarcoplasmic reticulum, each of which is controlled locally by single coassociated L-type Ca2+ channels ("local control theory of excitation-contraction coupling"). All prior studies on Ca2+ sparks, however, have been performed in single enzymatically dissociated heart cells under nonphysiological conditions. In order to understand the possible significance of Ca2+ sparks to normal working cardiac muscle, we used confocal microscopy to record Ca2+ sparks, spatially averaged [Ca2+]i transients and Ca2+ waves in individual cells of intact rat right ventricular trabeculae (composed of < 15 cells in cross section) microinjected with the Ca2+ indicator fluo 3 under physiological conditions ([Ca2+]o, 1 mmol/L; temperature, 33 +/- 1 degree C). Twitch force was recorded simultaneously. When stretched to optimal length (sarcomere length, 2.2 microns) and stimulated at 0.2 Hz, the trabeculae generated approximately equal to 700 micrograms of force per cell. Spatially averaged [Ca2+]i transients recorded from individual cells within a trabecula were similar to those recorded previously from single cells. The amplitude distribution of the peak ratio of Ca2+ sparks was bimodal, with maxima at ratios of 1.8 +/- 0.3 and 2.7 +/- 0.2 (mean +/- SD), respectively. The amplitude of the peak of Ca2+ sparks was approximately equal to 170 nmol/L. Ca2+ sparks occurred at a frequency of 12.0 +/- 0.8/s (mean +/- SEM) in line scans covering 94 sarcomeres. Ca2+ waves occurred randomly at a frequency of 0.57 +/- 0.08/s and propagated with a velocity of 29.5 +/- 1.7 microns/s. The extent of Ca2+ wave propagation was 3.9 +/- 0.3 sarcomere lengths (sarcomere length, 2.2 microns). Ca2+ sparks could be identified along the leading edge of the waves at intervals of 1.30 +/- 0.11 sarcomere length. Our observations suggest that (1) Ca2+ sparks, similar to those recorded in single cells, occur in trabeculae under physiological conditions and (2) coupling of Ca2+ spark generation between neighboring sites occurs and may lead to (3) the development of Ca2+ waves, which propagate under physiological conditions at a low velocity over limited distances. The results suggest that concepts of excitation-contraction coupling recently derived from isolated myocytes are applicable to intact cardiac trabeculae [corrected].
Aniline Compounds↗
Maximal actomyosin ATPase activity and in vitro myosin motility are unaltered in human mitral regurgitation heart failure.
Myofibrillar but not actomyosin ATPase is depressed in failing myocardium from patients with dilated cardiomyopathy. Since there is a similar depression of myofibrillar ATPase in mitral regurgitation myocardium, we investigated whether or not the hydrolytic and mechanical performances of myosin are altered by comparing the maximal actomyosin ATPase activity and the in vitro myosin motility of myocardial myosin from patients with mitral regurgitation heart failure with that of patients with normal ventricular function. The results show that there is no significant difference (P > .05) between nonfailing and failing values for either the maximal actomyosin ATPase activity (0.3 s-1.head-1) or the myosin motility (1 micron/s). These observations suggest that changes, other than in the myosin heavy chain, contribute to the altered myocardial performance in mitral regurgitation myocardium.
Actins↗