Mitochondrial calcium uptake in the perfused contracting rat heart and the influence of epinephrine on calcium exchange

Horn, Richard; Fyhn, Anne Birgitte; Haugaard, Niels

doi:10.1016/0005-2728(71)90112-5

Cited by 27 publications

(5 citation statements)

References 14 publications

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“…If this were true, it may very well be that hormones, vitamins and metabolites such as cyclic AMP which are known to influence cellular calcium may act on the exchange of calcium between cytoplasm and mitochondria rather than affecting directly the influx or efflux of calcium in and out of the cell (Kimberg & Goldstein, 1967;Horn, Fyhn & Haugaard, 1970;Rasmussen, 1970;Ahren, Hjalmarson & Isaksson, 1971;Bode, 1971 a, b;Bode, 19'72). This series of experiments may not bring the proof that they are literally relevant but they are certainly consistent with the view ~that mitochondria play an important role in the control of intracellular calcium.…”

Section: Discussionmentioning

confidence: 99%

Kinetic analysis of calcium movements in cell culture

Borle

1972

J. Membrain Biol.

118

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The distribution of intracellular calcium was determined in isolated kidney cells by kinetic analyses of 4SCa fluxes. Isotopic desaturation curves reveal an intracellular calcium compartment with a very slow time constant. The size of this calcium compartment is markedly increased by raising the extraceUular calcium, by increasing the extracellular phosphate and may contain up to 99 % of the intracellular exchangeable calcium. Accumulation of calcium in this pool is completely abolished by two specific inhibitors of mitochondrial calcium uptake, Antimycin A and Warfarin| These results suggest that this compartment represents a pool of calciura in the cell mitochondria. The sudden removal of phosphate from the medium immediately stimulates calcium efflux from the cell. Conversely, an increase in medium phosphate immediately inhibits calcium efflux. Both effects are rapidly reversible. Finally, calcium efflux from the cells is stimulated after the cells are exposed to low temperature suggesting that calcium transport out of the cell may be regulated by the cytoplasmic calcium activity. These experiments are consistent with the view that mitochondria play an important role in the control and regulation of cytoplasmic calcium activity and of calcium transport.

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Section: Discussionmentioning

confidence: 99%

Kinetic analysis of calcium movements in cell culture

Borle

1972

J. Membrain Biol.

118

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“…Cardiac mitochondria have been shown to accumulate in vitro large amounts of Ca++ in an energy-linked process (9,43,44) and to lower the Ca++ concentration in the medium to about 10-7 M (45, 46), a concentration required for the relaxation of the myofibrils in vivo (3,5,6,21). In addition, measurements of Ca++ distribution in subcellar fractions of the heart (10,37) and the use of various inhibitors in perfused heart preparations (12,13) have led to the conclusion that the energy-linked Ca++ movement of heart mitochondria plays a major role in the regulation of myocardial contractility. However, these and other studies have been regarded as too indirect and qualitative and have been criticized on the grounds of experimental approach and misinterpretation of the data obtained (3,7,(18)(19)(20).…”

Section: Mitochondrial Ca++ Uptake and Heart Relaxationmentioning

confidence: 99%

“…Although the involvement of calcium in the contractile cycle of skeletal and cardiac muscle is 756 THE JOURNAL OF GENERAL PHYSIOLOGY VOLUME 62, 973 . pages [756][757][758][759][760][761][762][763][764][765][766][767][768][769][770][771][772] similar (6)(7)(8), the role of sarcoplasmic reticulum in heart muscle is less clear and has been questioned by a number of investigators (9)(10)(11)(12)(13). The rationale of this questioning rests on the fact that the sarcoplasmic reticulum is poorly represented in heart (14,15) and shows reduced ability to accumulate Ca++ in vitro (1,3,5,16).…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, the mitochondria have been proposed to play an important role in the regulation of excitation contraction coupling of heart, by taking up and releasing significant amounts of Ca + + during the contractile cycle. Although during the last 10 years numerous reports have implicated the mitochondria as the relaxing factor in heart (9,10,(12)(13)17), most of these studies have been criticized on the grounds of the limitations of the technique used and misinterpretation of the data obtained (3,7,(18)(19)(20). Presently, the evidence for a major role of mitochondria in the regulation of the beat-to-beat Ca + + cycle in heart appears inconclusive (3,7).…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms for Intracellular Calcium Regulation in Heart

Scarpa

Graziotti

1973

The Journal of General Physiology

242

106

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Initial velocities of energy-dependent Ca + + uptake were measured by stopped-flow and dual-wavelength techniques in mitochondria isolated from hearts of rats, guinea pigs, squirrels, pigeons, and frogs. The rate of Ca + + uptake by rat heart mitochondria was 0.05 nmol/mg/s at 5 pM Ca + + and increased sigmoidally to 8 nmol/mg/s at 200 uM Ca + + . A Hill plot of the data yields a straight line with slope n of 2, indicating a cooperativity for Ca ++ transport in cardiac mitochondria. Comparable rates of Ca+ + uptake and sigmoidal plots were obtained with mitochondria from other mammalian hearts. On the other hand, the rates of Ca + + uptake by frog heart mitochondria were higher at any Ca + + concentrations. The half-maximal rate of Ca + + transport was observed at 30, 60, 72, 87, 92 MM Ca + + for cardiac mitochondria from frog, squirrel, pigeon, guinea pig, and rat, respectively. The sigmoidicity and the high apparent Km render mitochondrial Ca + + uptake slow below 10 puM. At these concentrations the rate of Ca ++ uptake by cardiac mitochondria in vitro and the amount of mitochondria present in the heart are not consistent with the amount of Ca + + to be sequestered in vivo during heart relaxation. Therefore, it appears that, at least in mammalian hearts, the energy-linked transport of Ca ++ by mitochondria is inadequate for regulating the beat-tobeat Ca + + cycle. The results obtained and the proposed cooperativity for mitochondrial Ca+ + uptake are discussed in terms of physiological regulation of intracellular Ca++ homeostasis in cardiac cells.

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“…The energy dependent accumulation of Ca" by mitochondria (for review see Chance, 1965: Lehninger, 1970) has led to the suggestion from several laboratories (Chance, 1965 ;Patriarca and Carafoli, 1968 ;Harigaya and Schwartz, 1969 ;Sulakhe and Dhalla, 1970 ;Horn et al ., 1971) that mitochondria may contribute to the regulation of intracellular free Ca` levels in cardiac muscle . Our long-term aim is to explore this question (Somlyo andSomlyo, 1970, 1971 ;Somlyo, 1972 ;Devine et al ., 1973) in smooth muscle .…”

Section: Introductionmentioning

confidence: 99%

Electron Microscopy and Electron Probe Analysis of Mitochondrial Cation Accumulation in Smooth Muscle

Somlyo¹,

Devine²,

Peters³

et al. 1974

The Journal of Cell Biology

130

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The contractile responses to barium and the ultrastructure and ionic composition of mitochondria were studied in vascular smooth muscle . In normal rabbit portal anterior mesenteric vein (PAMV) and main pulmonary artery (MPA) smooth muscle mitochondria were frequently associated with the surface vesicles . The Electron probe X-ray microanalysis also showed a highly significant (P < 0 .001) correlation of P with mitochondrial Ba, in an estimated elemental ratio of approximately 3 Ba/4 P . Mitochondrial granules were still prominent after block staining of the osmium-fixed, Ba-loaded PAMV, but electron probe microanalysis showed no Ba, but only U, emissions . Tissues incubated with strontium had electron-opaque mitochondrial granules and deposits in the sarcoplasmic reticulum . X-ray microanalysis of mitochondria containing granules showed the presence of characteristic Sr and Ca emissions . The presence of Sr was similarly verified in the sarcoplasmic reticulum . These findings indicate the energy dependent uptake of divalent cations, in association with phosphate, by mitochondria in vascular smooth muscle in situ and the possibility that mitochondria may contribute to the regulation of intracellular divalent cation levels in smooth muscle .

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Mitochondrial calcium uptake in the perfused contracting rat heart and the influence of epinephrine on calcium exchange

Cited by 27 publications

References 14 publications

Kinetic analysis of calcium movements in cell culture

Kinetic analysis of calcium movements in cell culture

Mechanisms for Intracellular Calcium Regulation in Heart

Electron Microscopy and Electron Probe Analysis of Mitochondrial Cation Accumulation in Smooth Muscle

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