The effects of inorganic phosphate and creatine phosphate on force production in skinned muscles from rat ventricle.

Kentish, Jonathan C.

doi:10.1113/jphysiol.1986.sp015952

Cited by 333 publications

(230 citation statements)

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“…The exact reasons for the differences in P i responsiveness between fibers and myofibril preparations are unclear but may involve the procedures used to reduce contaminating P i as described by Pate et al (30) and used in the myofibril experiments (36,37). Also, there is likely an inverse relationship between preparation diameter and force decline in response to added [P i ] because of greater accumulation of P i from myofibrillar ATPases (and thus higher baseline [P i ]) in thicker preparations (20,32). Regarding other contractile properties, added P i has been reported to increase k Pi (the rate constant of force decline after rapid increases in solution P i ) to a greater extent in cardiac myocyte preparations than in fast-twitch skeletal muscle fibers (2,41).…”

Section: Discussionmentioning

confidence: 99%

Inorganic phosphate speeds loaded shortening in rat skinned cardiac myocytes

Hinken¹,

McDonald²

2004

American Journal of Physiology-Cell Physiology

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Hinken, Aaron C., and Kerry S. McDonald. Inorganic phosphate speeds loaded shortening in rat skinned cardiac myocytes. Am J Physiol Cell Physiol 287: C500 -C507, 2004. First published April 14, 2004 10.1152/ajpcell.00049.2004.-Force generation in striated muscle is coupled with inorganic phosphate (Pi) release from myosin, because force falls with increasing P i concentration ([Pi]). However, it is unclear which steps in the cross-bridge cycle limit loaded shortening and power output. We examined the role of Pi in determining force, unloaded and loaded shortening, power output, and rate of force development in rat skinned cardiac myocytes to discern which step in the cross-bridge cycle limits loaded shortening. Myocytes (n ϭ 6) were attached between a force transducer and position motor, and contractile properties were measured over a range of loads during maximal Ca 2ϩ activation. Addition of 5 mM Pi had no effect on maximal unloaded shortening velocity (V o) (control 1.83 Ϯ 0.75, 5 mM added P i 1.75 Ϯ 0.58 muscle lengths/s; n ϭ 6). Conversely, addition of 2.5, 5, and 10 mM P i progressively decreased force but resulted in faster loaded shortening and greater power output (when normalized for the decrease in force) at all loads greater than ϳ10% isometric force. Peak normalized power output increased 16% with 2.5 mM added P i and further increased to a plateau of ϳ35% with 5 and 10 mM added P i. Interestingly, the rate constant of force redevelopment (ktr) progressively increased from 0 to 10 mM added Pi, with k tr ϳ360% greater at 10 mM than at 0 mM added Pi. Overall, these results suggest that the P i release step in the cross-bridge cycle is rate limiting for determining shortening velocity and power output at intermediate and high relative loads in cardiac myocytes. muscle mechanics; force-velocity relationship; cross-bridge cycle DURING MUSCLE CONTRACTION myosin cross bridges cyclically interact with actin in a process that is driven energetically by hydrolysis of ATP. The chemomechanical states in the crossbridge cycle have been investigated extensively in skinned muscle fiber preparations, and the transition rates between these states are qualitatively similar to rates derived from muscle protein studies in solution (15). A working model for the chemomechanical steps in the cross-bridge cycle is shown in Fig. 1 (40), which is based on extensive work in the field (for reviews see Refs. 3 and 15). According to this model, the transition from weak-binding, non-force-generating cross bridges to strong-binding, forcegenerating states is associated with the release of inorganic phosphate (P i ) (steps 3-5, Fig. 1; Ref. 16). Force generation is maintained through the release of ADP (step 6, Fig. 1; Refs. 6 and 22), which is followed by binding of ATP and subsequent cross-bridge detachment. The binding of ATP and its hydrolysis are thought to be relatively fast processes in skinned fibers (9,14,23). Thus the rate-limiting step in the cross-bridge cycle is thought to occur after ATP hydrolysis, either during an ...

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Section: Discussionmentioning

confidence: 99%

Inorganic phosphate speeds loaded shortening in rat skinned cardiac myocytes

Hinken¹,

McDonald²

2004

American Journal of Physiology-Cell Physiology

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“…Recent evidence suggests that changing the diffusion coefficients within the membrane can change the maximal rate of electron transport, indicating that ubiquinone (and possibly cytochrome c) diffusion may partially limit this rate (Chazotte & Hackenbrock, 1988aHackenbrock & Gupte, 1988 (Cooke & Pate, 1985;Kentish, 1986), and the contractile function and ATP use of perfused heart can be sensitive to the AGp (Kammermeier et al, 1982;Kupriyanov et al, 1991). However, in the heart in vivo Kim et al (1991) found that raising the AGP by increasing mitochondrial NADH supply did not increase respiration or contractile activity, indicating that mitochondrial processes had no significant flux control in heart.…”

Section: Application Of Metabolic Control Theorymentioning

confidence: 99%

Control of respiration and ATP synthesis in mammalian mitochondria and cells

Brown

1992

Biochemical Journal

564

308

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We have seen that there is no simple answer to the question ‘what controls respiration?’ The answer varies with (a) the size of the system examined (mitochondria, cell or organ), (b) the conditions (rate of ATP use, level of hormonal stimulation), and (c) the particular organ examined. Of the various theories of control of respiration outlined in the introduction the ideas of Chance & Williams (1955, 1956) give the basic mechanism of how respiration is regulated. Increased ATP usage can cause increased respiration and ATP synthesis by mass action in all the main tissues. Superimposed on this basic mechanism is calcium control of matrix dehydrogenases (at least in heart and liver), and possibly also of the respiratory chain (at least in liver) and ATP synthase (at least in heart). In many tissues calcium also stimulates ATP usage directly; thus calcium may stimulate energy metabolism at (at least) four possible sites, the importance of each regulation varying with tissue. Regulation of multiple sites may occur (from a teleological point of view) because: (a) energy metabolism is branched and thus proportionate regulation of branches is required in order to maintain constant fluxes to branches (e.g. to proton leak or different ATP uses); and/or (b) control over fluxes is shared by a number of reactions, so that large increases in flux requires stimulation at multiple sites because each site has relatively little control. Control may be distributed throughout energy metabolism, possibly due to the necessity of minimizing cell protein levels (see Brown, 1991). The idea that energy metabolism is regulated by energy charge (as proposed by Atkinson, 1968, 1977) is misleading in mammals. Neither mitochondrial ATP synthesis nor cellular ATP usage is a unique function of energy charge as AMP is not a significant regulator (see for example Erecinska et al., 1977). The near-equilibrium hypothesis of Klingenberg (1961) and Erecinska & Wilson (1982) is partially correct in that oxidative phosphorylation is often close to equilibrium (apart from cytochrome oxidase) and as a consequence respiration and ATP synthesis are mainly regulated by (a) the phosphorylation potential, and (b) the NADH/NAD+ ratio. However, oxidative phosphorylation is not always close to equilibrium, at least in isolated mitochondria, and relative proximity to equilibrium does not prevent the respiratory chain, the proton leak, the ATP synthase and ANC having significant control over the fluxes. Thus in some conditions respiration rate correlates better with [ADP] than with phosphorylation potential, and may be relatively insensitive to mitochondrial NADH/NAD+ ratio.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…However, dissociation of functional parameters from myocardial intracellular phosphate levels as occurred during this study is fairly specific to the particular study conditions (2,(26)(27)(28). Intracellular phosphate as well as pH have been implicated as regulators of contractile function during hypoxia or ischemia (24,27,29). The codependence of these factors in modulation of myocardial force generated during oxygen deprivation is a subject of controversy (30).…”

Section: F102(%)mentioning

confidence: 99%

“…This mechanism would diminish Ca2' activated maximal force (29,32). Conceivably, catecholamine stimulation during hypoxia would counter such an effect by increasing Ca2+ sarcoplasmic reticulum release and recycling, as well as possibly influencing myofibril sensitivity to Ca2+ (33).…”

Section: F102(%)mentioning

confidence: 99%

“…The codependence of these factors in modulation of myocardial force generated during oxygen deprivation is a subject of controversy (30). Studies performed in perfused hearts (16), and in skinned rat ventricular myocytes (29) indicate that increases in intracellular phosphate cause a decline in maximal Ca2" activated force. This relationship appears to be pH independent, at least in skinned fiber studies.…”

Section: F102(%)mentioning

confidence: 99%

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Relation of myocardial oxygen consumption and function to high energy phosphate utilization during graded hypoxia and reoxygenation in sheep in vivo.

Portman¹,

Standaert²,

Ning³

1995

J. Clin. Invest.

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IntroductionThis study investigates the relation between myocardial oxygen consumption (MV 02), function, and high energy phos- Severe hypoxia ultimately leads to contractile failure, which is attributed to an imbalance between myocardial oxygen supply and demand (1)(2)(3)(4). Sudden extreme oxygen deprivation causes rapid depletion of energy stores in the form of the high energy phosphates, phosphocreatine, and ATP, as well as accumulation of ATP hydrolysis products. In isolated myocytes (5) and buffer-perfused hearts (5, 6) anoxia or hypoxia results in a reduced oxidative phosphorylation rate. Myocardial respiration wanes despite increasing ADP and intracellular phosphate (Pi),' which both stimulate mitochondrial ATP production under aerobic conditions. The intact animal generally maintains or increases myocardial oxygen consumption during early or moderate hypoxia (7-9). Small decreases in myocardial phosphocreatine content with no depletion of the cytosolic ATP pool have been documented during moderate hypoxic conditions (10, 11). However, myocardial oxygen consumption rates have not been directly measured during periods of rapid high energy phosphate depletion and repletion in the intact animal. The purpose of this study was to examine the relation between myocardial oxygen consumption, function, and high energy phosphates during severe hypoxia and reoxygenation in vivo. Additionally, rephosphorylation parameters were measured to determine if evidence of respiratory uncoupling or mitochondrial damage occurs during reoxygenation in vivo. Graded hypoxia was performed in an effort to gradually reduce arterial oxygen tension to attain the P02 at which high energy phosphate stores rapidly decreased. Highly time-resolved 31P nuclear magnetic resonance (NMR) spectroscopy enabled monitoring of myocardial phosphates throughout hypoxia and recovery with simultaneous measurement of oxygen consumption. Consequently, these measurements enhanced analysis of mitochondrial function in vivo during reoxygenation. MethodsAnimal preparation. Animals used in this study were handled in accordance with institutional and National Institutes of Health animal care and use guideline. Sheep between 30 and 70 d old (mean 47 d±6.8) were sedated with an intramuscular injection of 10 mg/kg ketamine, and 0.2-0.4 mg/kg xylazine, intubated, and then ventilated (C-900 pediatric ventilator; Siemens Corp., Schaumberg, IL) with room air and oxygen, followed by an intravenous dose of alpha-chloralose (40 mg/ kg). Femoral arterial cannulation was performed for monitoring systemic blood pressure and sampling blood. Arterial pH was maintained between 7.35 and 7.45 by adjustment of ventilatory tidal volume and 1. Abbreviations used in this paper: FIo2, fractional inspiratory oxygen

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The effects of inorganic phosphate and creatine phosphate on force production in skinned muscles from rat ventricle.

Cited by 333 publications

References 39 publications

Inorganic phosphate speeds loaded shortening in rat skinned cardiac myocytes

Inorganic phosphate speeds loaded shortening in rat skinned cardiac myocytes

Control of respiration and ATP synthesis in mammalian mitochondria and cells

Relation of myocardial oxygen consumption and function to high energy phosphate utilization during graded hypoxia and reoxygenation in sheep in vivo.

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