Excitation-contraction coupling in heart muscle: Membrane control of development of tension

Morad, Martin; Goldman, Yale E.

doi:10.1016/0079-6107(73)90008-4

Cited by 313 publications

(296 citation statements)

References 124 publications

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“…The patients were divided into three groups on the basis of the information presented in table 1 and figure 1. The first group (A, nine patients) were classified as having "normal" hearts based on the following criteria: pulmonary arterial chest x-ray cardiothoracic ratio less than 0.…”

Section: Methodsmentioning

confidence: 99%

Relationships between beat-to-beat interval and the strength of contraction in the healthy and diseased human heart.

Seed¹,

Noble²,

Walker³

et al. 1984

Circulation

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Twenty-six adult patients, classified by clinical and catheter criteria into groups of those with normal and abnormal left ventricular function, were studied during cardiac catheterization. Right heart pacing was established, and left ventricular dP/dt was measured with end-catheter manometers. By varying the interval preceding a test beat after periods of steady pacing it was confirmed that recovery of left ventricular mechanical function (maximum dP/dt) occurs approximately 800 msec (optimum interval) after a beat. The augmentation of maximum dP/dt of the first 2 beats after an extrasystole, each spaced at the optimum interval, was also studied; the amount of potentiation was varied by alterations in extrasystolic interval. Potentiation decayed from the first to the second postextrasystolic beat with a ratio that was fixed in each individual patient. The ratio (recirculation fraction) was higher in patients with normal than in those with abnormal left ventricular function (mean SD 0.52 0.10 vs 0.37 ± 0.11, p < .005). There was an inverse relationship between this ratio and the degree of potentiation of the first postextrasystolic beat (r = .80, p < .001). We postulate a disturbance of excitation-contraction coupling mechanisms to explain these effects. Circulation 70, No. 5, 799-805, 1984. ACCORDING TO current theories regarding excitation-contraction coupling,' calcium ions that enter the myocardial cells during the action potential and those that are taken up from the contractile apparatus during relaxation of contraction enter an intracellular store. This calcium is released on a subsequent depolarization, and thus some of the released calcium is "recirculated" from the previous beat. We Our first objective in this study was to measure the recirculation fraction in man. Since a disturbance of excitation-contraction coupling, and thus of intracellular calcium handling, might underlie malfunction of cardiac muscle, our second objective was to compare this recirculation fraction in patients with normal and abnormal myocardial function. MethodsPatients. Twenty-six subjects were studied during the course of diagnostic cardiac catheterization. The indications for catheterization included breathlessness, chest pain, and arrhythmias. Informed consent was obtained from the subjects before the study, which had been approved by the ethical committees of the respective institutions. Patients were studied while supine and after an overnight fast.The patients were divided into three groups on the basis of the information presented in table 1 and figure 1. The first group (A, nine patients) were classified as having "normal" hearts based on the following criteria: pulmonary arterial chest x-ray cardiothoracic ratio less than 0.

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Section: Methodsmentioning

confidence: 99%

Relationships between beat-to-beat interval and the strength of contraction in the healthy and diseased human heart.

Seed¹,

Noble²,

Walker³

et al. 1984

Circulation

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“…The immediate origin of this Ca2" has been the subject of much controversy (for review, see refs. [2][3][4][5]. Much of it may come from cellular stores.…”

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confidence: 99%

Measurement of rapidly exchangeable cellular calcium in the perfused beating rat heart.

Hunter¹,

Haworth²,

Berkoff³

1981

Proc. Natl. Acad. Sci. U.S.A.

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Although Ca2+ has long been known to play a vital role in excitation-contraction coupling in the heart, investigation of the details of this role has been hampered by the experimental difficulty of measuring Ca2+ movements through the different compartments ofthe cell. A major problem has been to distinguish the relatively small amount of rapidly exchangeable cellular Ca2+ from the large amount ofvascular and interstitial Ca2+. We report here a method that overcomes this problem. Rat Excitation ofthe heart induces an increase in cellular free Ca2", which then triggers myocardial contraction (1). The immediate origin of this Ca2" has been the subject of much controversy (for review, see refs. 2-5). Much of it may come from cellular stores. However, attempts to measure myocardial cellular Ca2" have met with limited success. Ca2' influx during excitation of the myocardial cell has been demonstrated electrophysiologically (6-8), although the extent of this influx is still in dispute.With the aid of aequorin, a Ca2+-sensitive fluorescent probe, a beat-to-beat fluctuation ofcytoplasmic levels offree Ca2+ has been observed in the frog heart (1). However, the interpretation ofexperiments designed to measure Ca2+ fluxes by using 'Ca2+ has been equivocal. Experiments with heart tissue have shown beat-dependent 'Ca2+ uptake (9-14) but of a magnitude far greater than found in cultures of beating neonatal cells (15). In all cases, a major problem has been that the cellular Ca2+ represents such a small fraction of the total Ca2+ in the tissue that it is almost impossible to detect. Furthermore, cellular Ca2+ fluxes occur on a time scale similar to that of vascular and interstitial washout time, so that although kinetic analysis of 'Ca2+ washout from the whole heart shows many pools (16, 17), the pool of interest is still difficult to distinguish from the extracellular pools. We have circumvented this problem by using the well-known fact that active processes have a much higher Q1o than simple diffusion. Thus, by cooling the heart after labeling with perfusate containing 'Ca2 , the cellular '5Ca2+ becomes trapped. The high background 'Caa2+ from vascular and interstitial spaces is then removed by perfusion at 6°C, so that cellular Ca2+ can readily be detected be releasing it with a second warm perfusion. METHODSLabeling of Heart with 'Ca"+. Retired female breeder rats (Sprague-Dawley) were anesthetized by intraperitoneal injection of thiamylal (100 mg/kg). The heart was excised, and cannulas were placed in the aorta and pulmonary vein. Incisions were made in the pulmonary artery and the right atria to allow adequate flow. The basal perfusate was 118 mM NaCV25 mM NaHCOV4.7 mM KCV1.2 mM KH2POd1.2 mM MgSO411 mM glucose/2.5 mM CaCl2, pH 7.4. It was bubbled with 95% 02/5% Co2 and warmed to 37°C. The heart was perfused for 10 sec through the pulmonary vein cannula to wash out any air bubbles. Then it was perfused for the remainder ofthe perfusion period through the aorta. The height ofthe reservoir was 65 cm above the hea...

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“…The slow adaptation to the new condition was clearly demonstrated by LONDON and KRUEGER (1986) in the single perfused cell experiment of an adult guinea pig ventricle. On the other hand, the frog ventricle is known to respond rapidly to the change in the membrane potential duration and shows little change in the following beats (MORAD and GOLDMAN, 1973). In that sense the cells shown in Fig.…”

Section: Discussionmentioning

confidence: 90%

Relationship between contraction strength and stimulation frequency in cultured chick embryonic heart cells.

Toyota¹,

Matsumura²

1989

Jpn.J.Physiol

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Membrane potential and contraction were investigated in cultured chick embryonic heart cell aggregate. The cells were stimulated through the intracellular microelectrode, and the contraction of the cell aggregate was measured from the shortening of the diameter. The contraction decreased if the stimulation frequency was raised in the range between 20/min and 100/min; namely, the negative relationship between contraction strength and stimulation frequency. The peak action potential or plateau duration was not affected by the change in the stimulation frequencies unless they exceeded 60/min, but they were shortened at frequencies higher than 75/min. In the latter case, the decrease of contration strength was related to the shortening of plateau duration. If the stimulation frequency was lowered suddenly, the following contraction was transiently increased without any noticeable change in the shape of the action potential. When TTX was added (3-10 x 10-6M) , the rate of the spontaneous activity was reduced, which made it possible to study the contraction strength at low stimulation frequencies. In TTX medium, similar to the observations in the control medium, the relationship between contraction strength and stimulation frequency was also negative. In the medium containing TTX plus verapamil (5-9 x 10-' M), the peak action potential was inhibited during the repetitive stimulation dependently on the stimulation frequency, accompanied by the concomitant decrease of contraction strength. These results suggest that the negative inotropic effect of the stimulation frequency is caused in part by the change in Ca2+ inflow.

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Excitation-contraction coupling in heart muscle: Membrane control of development of tension

Cited by 313 publications

References 124 publications

Relationships between beat-to-beat interval and the strength of contraction in the healthy and diseased human heart.

Relationships between beat-to-beat interval and the strength of contraction in the healthy and diseased human heart.

Measurement of rapidly exchangeable cellular calcium in the perfused beating rat heart.

Relationship between contraction strength and stimulation frequency in cultured chick embryonic heart cells.

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