Maturation of Calcium Transport in Cardiac Sarcoplasmic Reticulum

Mahony, Lynn

doi:10.1203/00006450-198811000-00020

Cited by 39 publications

(14 citation statements)

References 17 publications

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“…In addition, ryanodine's abolition of phasic tension induced by Ca2+ loading suggests that conditioning clamp protocols augment phasic tension by increasing the Ca2+ content of the SR. Consequently, it may be the case that the mechanism for release of Ca2+ from the SR is present and functional in the newborn period, but participation of the SR in tension development is reduced because of a diminished SR Ca2+ content. This speculation is consistent with the decreased ability to accumulate Ca2+ demonstrated in vesicles of SR isolated from immature lamb, guinea pig, and rabbit (19)(20)(21). However, it should be recognized that the Ca2+ content of the SR may be higher at physiologic heart rates and temperatures than under the experimental conditions used in these studies and those of other investigators.…”

Section: Implications For Generation Of Phasic Component Of Tensionsupporting

confidence: 54%

A Diminished Role for the Sarcoplasmic Reticulum in Newborn Myocardial Contraction: Effects of Ryanodine

Klitzner

Friedman

1989

Pediatr Res

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ABSTRACT. Ryanodine, known to reduce Ca2+ release from the sarcoplasmic reticulum (SR), was used in conjunction with the single sucrose gap voltage clamp technique to study excitation-contraction coupling in papillary muscles isolated from newborn and adult rabbits. Ryanodine altered the components of voltage clamp-induced tension in the adult producing a pattern that closely resembled the normal newborn. The phasic component of tension in mature myocardium was markedly and significantly reduced by ryanodine. In addition, ryanodine significantly altered the voltage dependence of this component of tension, suggesting a change in its mechanism of generation. The appearance of a prominent phasic component of tension, absent normally, but produced in the newborn by CaZ' loading, was also abolished by ryanodine. These results support previous proposals that the phasic component of voltage clamp-induced tension in mammalian myocardium is produced by the release of Ca2+ from the SR. In the newborn, ryanodine caused a significantly smaller decrease in the ratio of phasic to tonic tension than in the adult, suggesting a much less significant role for the SR in excitation-contraction coupling in the younger age group. Although ryanodine had a significant effect on phasic tension, no alteration in the amplitude or voltage dependence of tonic tension, generated by transmembrane Ca2+ influx, could be demonstrated in either newborn or adult heart. This investigation suggests that in newborn myocardium, Ca2+ release from the SR plays a negligible role in excitation-contraction coupling, which depends, rather, on the influx of Ca2+ from the extracellular space. ( characterized by an early peak of tension (phasic tension) which then relaxes to a steady state level (1, 2). It has been postulated that the lack of phasic tension in the immature myocardium reflects structural and functional immaturity of the t-tubules and SR ( 1, 3). To further investigate this hypothesis, experiments were conducted using the alkaloid ryanodine in an attempt to selectively eliminate Ca2+ release from the SR. Ryanodine has been shown to diminish release of Ca2+ from the SR, either by directly inhibiting Ca2+ release mechanisms (4-6), or by enhancing Ca2+ emux, resulting in Ca2+ depletion of the SR (7, 8), with little or no effect on the amplitude of membrane Ca2+ currents (9, 10) or the function of contractile proteins (1 I). It has been demonstrated previously that the negative inotropic effect of ryanodine is less pronounced in immature than mature mammalian myocardium (1 2-14) suggesting that it may be a useful tool in studying the changes which occur in the mechanisms of myocardial excitation-contraction coupling with development. MATERIALS AND METHODSPreparation. Right ventricular papillary muscles, 0.3-0.7 mm in diameter, were dissected from seven newborn (0-10 days) and six adult New Zealand White rabbits. Muscles were isolated and placed in a three compartment single sucrose gap, voltage clamp chamber. The tendinous end of the papillary muscl...

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Section: Implications For Generation Of Phasic Component Of Tensionsupporting

confidence: 54%

A Diminished Role for the Sarcoplasmic Reticulum in Newborn Myocardial Contraction: Effects of Ryanodine

Klitzner

Friedman

1989

Pediatr Res

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“…The need for a higher filling pressure to optimize myofilament alignment might explain our finding of improved economy of force production at high end-diastolic pressures in the newborn heart. Second, the newborn myocardium has been noted to have an immature sarcoplasmic reticulum, and consequently has a greater reliance on the sarcolemma for excitation-contraction coupling (6). We speculate that differences between the two membranes in the coupling of ATP to calcium flux might produce differences in the efficiency of force development.…”

Section: Resultsmentioning

confidence: 99%

“…Mahony (6) demonstrated that there was a marked increase in the coupling of sarcoplasmic reticulum Ca2+ transport to ATP hydrolysis during maturation of the heart. In sheep, this maturational process seems to continue through the 8th wk of life.…”

mentioning

confidence: 99%

Force and Oxygen Consumption in the Immature Rabbit Heart

Parrish

Farrar

1990

Pediatr Res

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ABSTRACT. We speculated that there are important agerelated differences in the economy of left ventricular force development in the isolated heart. To assess this, we evaluated oxygen consumption and force development in newborn (less than 1 wk old) (n = 26), juvenile (4-6 wk old) (n = 26), and adult (5-7 mo old) (n = 26) isolated, isovolumic rabbit hearts. Measurements were obtained with three different interventions, including 1 ) changes in heart rate, 2) inotropic stimulation with isoproterenol, and 3) changes in end-diastolic pressure. We found no significant baseline differences in the economy of force development. However, when heart rate was increased by 20%, the force/oxygen consumption ratio (economy) increased in newborn hearts by approximately 37%, whereas there was a decrease in juvenile and adult hearts of -27%. In addition, with increases in end-diastolic pressure above 10 mm Hg, newborn hearts increased their force/myocardial oxygen consumption ratio to 300% of the baseline value, whereas adults increased to only 160% of baseline. Isoproterenol produced no significant age-related differences in the force/myocardial oxygen consumption ratio. We conclude that there are important age-related differences in the economy of left ventricular force development in this model, but these differences are apparent only at higher heart rates and end-diastolic pressures. (Pediatr Res 27: 476-482,1990) of myosin isozyme V, was greatest in the newborn and lowest in the adult (3). Furthermore, Kissling and Rupp (5) have demonstrated in rats that the degree of catecholamine-induced increase in myocardial oxygen consumption depends on the isoenzyme pattern of myosin. Perhaps the force/oxygen consumption ratio also changes with alterations in myocardial isoenzymes, although there are no data to confirm this.We know that the newborn heart has a less mature sarcoplasmic reticulum than the adult. Mahony (6) demonstrated that there was a marked increase in the coupling of sarcoplasmic reticulum Ca2+ transport to ATP hydrolysis during maturation of the heart. In sheep, this maturational process seems to continue through the 8th wk of life. We speculated that this maturation of calcium coupling ratio might manifest as a developmental increase in the economy of myocardial force development.Thus, there are fundamental biochemical differences between the newborn and adult myocardium. Differences in myosin isozyme or sarcoplasmic reticulum could conceivably alter the coupling of ATP hydrolysis to force generation. Therefore, we hypothesized that there might be important maturational changes in the economy of myocardial force generation independent of changes in ventricular pressure or volume. To further assess this, we evaluated oxygen consumption and force development in newborn, juvenile, and adult isolated, isovolumic rabbit hearts. Abbreviations MATERIALS AND METHODSdP/dt, change in pressure per unit time Methods. Standard techniques for an isolated, isovolumic rabbit heart preparation were modified primarily to isolat...

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“…*, the presence of that intervention significantly increases heart rate. * The coefficients b (see Table I of the sacroplasmic reticulum (17)(18)(19)(20)(21), and underdevelopment of the l3-receptorjadenylate cyclase complex (22,23). However, mechanisms that are thought to accelerate myocardial maturity at birth, such as surges in thyroid hormone (23), cannot be functional in this preparation, and isoproterenol, the only intervention that should increase contractility in a manner similar to the postnatal catecholamine surge (37), only modestly increased output (36%).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies point to myocardial immaturity: incomplete development of sarcomeres (17)(18)(19)(20)(21), decreased functioning of {J-receptors (22,23), and myofibrillar disarray (24,25) have all been implicated. Although fetal myocardium is certainly immature relative to that of the adult, none of these factors have been shown to change immediately at birth.…”

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confidence: 99%

In Utero Ventilation Augments the Left Ventricular Response to Isoproterenol and Volume Loading in Fetal Sheep

et al. 1991

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The basis of this limitation in the ability of the fetal left ventricle to greatly increase output (systolic performance) is controversial. Several studies point to myocardial immaturity: incomplete development of sarcomeres (17-21), decreased functioning of {J-receptors (22, 23), and myofibrillar disarray (24,25) have all been implicated. Although fetal myocardium is certainly immature relative to that of the adult, none of these factors have been shown to change immediately at birth. In addition, many indices of systolic performance are increased in the newborn left ventricle relative to that of the adult (11,12), so that myocardial immaturity may not necessarily be associated with impaired ventricular function. It is remarkable that both the prematurely born animal (26-28) and human (29), which have not been exposed to prenatal hormone surges and labor to accelerate myocardial maturation, are capable of greatly increasing left ventricular output in response to a patent ductus arteriosus. In addition, recent studies of fetal sheep undergoing oxygen ventilation in utero have shown a doubling of left ventricular output (3,30), and other determinants of output such as septal compliance (31) have been shown to change in the perinatal period.Thus, left ventricular output may be limited in the fetus more because of its "circulatory environment" (the combination of a parallel circulation with central shunts, a dominant hypertrophied right ventricle that ejects more output and fills under similar pressures, a pulmonary vascular bed that is markedly constricted and that returns a very limited amount of blood to the left atrium and ventricle, and a highly compliant fetoplacental vascular bed that can absorb increases in volume that would otherwise increase left ventricular filling volume) than because of myocardial immaturity. For example, the fetal left ventricle has a very limited ability to increase output via the Frank-Starling mechanism (13), with a plateau occurring at 5-7 mm Hg. However, Hawkins et at.(32) have shown that some of this limitation is caused by a concomitant increase in afterload; if afterload is controlled, left ventricular output continues to rise at filling pressures of 10 mm Hg. In addition, high right ventricular filling and ejecting pressures may constrain left ventricular performance both in diastole and systole (33-36).We undertook the present study to determine whether the near-term (approximately 0.9 gestation) fetal left ventricle, functioning in a simulated "postnatal circulatory environment" (abolition of most central shunts with a small left to right shunt through the ductus arteriosus, a dominant left ventricle ejecting somewhat more blood than the right under higher filling pressures, a dilated pulmonary vascular bed returning a large amount of blood to the left atrium and ventricle, and a decrease in the fetoplacental vascular bed), is capable of increasing its output to levels similar to those seen in the newborn. We simulated the immediate postnatal circulatory environment in ute...

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Maturation of Calcium Transport in Cardiac Sarcoplasmic Reticulum

Cited by 39 publications

References 17 publications

A Diminished Role for the Sarcoplasmic Reticulum in Newborn Myocardial Contraction: Effects of Ryanodine

A Diminished Role for the Sarcoplasmic Reticulum in Newborn Myocardial Contraction: Effects of Ryanodine

Force and Oxygen Consumption in the Immature Rabbit Heart

In Utero Ventilation Augments the Left Ventricular Response to Isoproterenol and Volume Loading in Fetal Sheep

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