Cytosolic Free Magnesium Levels in Ischemic Rat Heart

Murphy, Elizabeth; Steenbergen, Charles; Levy, Louis; Raju, Bore; London, Robert E.

doi:10.1016/s0021-9258(18)83593-1

Cited by 215 publications

(40 citation statements)

References 30 publications

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“…Experimental data suggest that, under metabolic inhibition, free intracellular Mg 2ϩ concentration may increase to 2-6 mM (Kirkels et al, 1989;Murphy et al, 1989;Carmeliet, 1999). In our simulations, diastolic Mg 2ϩ increased from 1 to ϳ2.25 mM when [ATP] tot /[ADP] tot was unity and to 7.44 mM when ATP and ADP were zero.…”

Section: Metabolic Inhibitionmentioning

confidence: 58%

“…The corresponding off-rate constants were obtained from the known values of equilibrium dissociation constants (K D CaADP , K D MgATP , K D MgADP ). It is known that free Mg 2ϩ in cardiac cells is between 0.5 and 2 mM (Bers, 1991;Leyssens et al, 1996;Carmeliet, 1999;Murphy et al, 1989). Here we assume that, at equilibrium, free Mg 2ϩ concentrations in the subspace and myoplasm do not differ, a value of 1 mM was used for both (see Table 3).…”

Section: Methods and Model Parametersmentioning

confidence: 99%

“…Experimental studies have demonstrated that block of oxidative metabolism and a fall in [ATP] tot /[ADP] tot ratio cause important changes in ion concentrations ([ [Mg 2ϩ ] i ) and have important effects on channels and carriers (Murphy et al, 1989;Marban et al, 1990;Wagner et al, 1990;Isenberg et al, 1993;Wilde and Aksnes, 1995;Carmeliet, 1999;Huser et al, 2000). Ch'en et al (1998) reported that, while creatine phosphate is present, total ATP and ADP concentrations remain constant, at ϳ7 and ϳ0 mM, respectively.…”

Section: Ion and Buffer Concentrations And Ion Currents During Metabolic Inhibitionmentioning

confidence: 99%

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Model Study of ATP and ADP Buffering, Transport of Ca2+ and Mg2+,and Regulation of Ion Pumps in Ventricular Myocyte

Michailova

McCulloch

2001

Biophysical Journal

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We extended the model of the ventricular myocyte by Winslow et al. (Circ. Res 1999, 84:571-586) by incorporating equations for Ca(2+) and Mg(2+) buffering and transport by ATP and ADP and equations for MgATP regulation of ion transporters (Na(+)-K(+) pump, sarcolemmal and sarcoplasmic Ca(2+) pumps). The results indicate that, under normal conditions, Ca(2+) binding by low-affinity ATP and diffusion of CaATP may affect the amplitude and time course of intracellular Ca(2+) signals. The model also suggests that a fall in ATP/ADP ratio significantly reduces sarcoplasmic Ca(2+) content, increases diastolic Ca(2+), lowers systolic Ca(2+), increases Ca(2+) influx through L-type channels, and decreases the efficiency of the Na(+)/Ca(2+) exchanger in extruding Ca(2+) during periodic voltage-clamp stimulation. The analysis suggests that the most important reason for these changes during metabolic inhibition is the down-regulation of the sarcoplasmic Ca(2+)-ATPase pump by reduced diastolic MgATP levels. High Ca(2+) concentrations developed near the membrane might have a greater influence on Mg(2+), ATP, and ADP concentrations than that of the lower Ca(2+) concentrations in the bulk myoplasm. The model predictions are in general agreement with experimental observations measured under normal and pathological conditions.

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Section: Metabolic Inhibitionmentioning

confidence: 58%

Section: Methods and Model Parametersmentioning

confidence: 99%

Section: Ion and Buffer Concentrations And Ion Currents During Metabolic Inhibitionmentioning

confidence: 99%

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Model Study of ATP and ADP Buffering, Transport of Ca2+ and Mg2+,and Regulation of Ion Pumps in Ventricular Myocyte

Michailova

McCulloch

2001

Biophysical Journal

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“…The supporting evidence for this decrease was the effect of intracellular Mg 2C on the RyR channel. Mg 2C has been reported to be in the sub-millimolar range (Page & Polimeni 1972;Garfinkel et al 1986;Kirkels et al 1989;Murphy et al 1989). Mg 2C binds two different sites on the RyR, acting as an antagonist to the high-affinity Ca 2C activation site and as an agonist at the low-affinity Ca 2C inactivation site (Meissner et al 1997;Murayama et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Simulation of Ca ²⁺ -activated Cl ⁻ current of cardiomyocytes in rabbit pulmonary vein: implications of subsarcolemmal Ca ²⁺ dynamics

Leem

Kim

et al. 2006

Phil. Trans. R. Soc. A.

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In recent studies, we recorded transiently activated outward currents by the application of three-step voltage pulses to induce a reverse mode of Na+-Ca2+ exchange (NCX). We found that these currents were mediated by a Ca2+-activated Cl- current. Based on the recent reports describing the atrial Ca2+ transients, the Ca2+ transient at the subsarcolemmal space was initiated and then diffused into the cytosolic space. Because the myocardium in the pulmonary vein is an extension of the atrium, the Ca2+-activated Cl- current may reflect the subsarcolemmal Ca2+ dynamics. We tried to predict the subsarcolemmal Ca2+ dynamics by simulating these current traces. According to recent reports on the geometry of atrial myocytes, we assumed that there were three compartments of sarcoplasmic reticulum (SR): a network SR, a junctional SR and a central SR. Based on these structures, we also divided the cytosolic space into three compartments: the junctional, subsarcolemmal and cytosolic spaces. Geometry information and cellular capacitance suggested that there were essentially no T-tubules in these cells. The basic physical data, such as the compartmental volumes, the diffusion coefficients and the stability coefficients of the Ca2+ buffers, were obtained from the literature. In the simulation, we incorporated the NCX, the L-type Ca2+ channel, the rapid activating outward rectifier K+ channel, the Na+-K+ pump, the SR Ca2+-pump, the ryanodine receptor, the Ca2+-activated Cl- channel and the dynamics of Na+, K+, Ca2+ and Cl-. In these conditions, we could successfully reconstruct the Ca2+-activated Cl- currents. The simulation allowed estimation of the Ca2+ dynamics of each compartment and the distribution of the Ca2+-activated Cl- channel and the NCX in the sarcolemma on the junctional or subsarcolemmal space.

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“…Yeast samples (IMX1844) were harvested as previously described [121] Based on the cytosolic concentrations described in literature, we have designed an assay medium that was as close as possible to the in vivo situation, whilst at the same time experimentally feasible. The standardized in vivo-like assay medium contained 150 mM potassium [128][129][130][131], 5 mM phosphate [128,132], 15 mM sodium [128,133], 155 mM chloride [134,135], 0.5 mM calcium, 0.5 mM free magnesium [128,136,137] and 0.5-10.5 mM sulfate. For the addition of magnesium, it was taken into account that ATP and ADP bind magnesium with a high affinity.…”

Section: Cell-free Extract Preparation and Vmax Enzyme Assaysmentioning

confidence: 99%

A yeast with muscle doesn’t run faster: full humanization of the glycolytic pathway in Saccharomyces cerevisiae

Boonekamp

Knibbe

Vieira-Lara

et al. 2021

Preprint

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While transplantation of single genes in yeast plays a key role in elucidating gene functionality in metazoans, technical challenges hamper the humanization of full pathways and processes. Empowered by advances in synthetic biology, this study demonstrates the feasibility and implementation of full humanization of glycolysis in yeast. Single gene and full pathway transplantation revealed the remarkable conservation of both glycolytic and moonlighting functions and, combined with evolutionary strategies, brought to light novel, context-dependent responses. Remarkably, human hexokinase 1 and 2, but not 4, required mutations in their catalytic or allosteric sites for functionality in yeast, while hexokinase 3 was unable to complement its yeast ortholog. Comparison with human tissues cultures showed the preservation of turnover numbers of human glycolytic enzymes in yeast and human cell cultures. This demonstration of transplantation of an entire, essential pathway paves the way to the establishment of species, tissue and disease-specific metazoan models.

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Cytosolic Free Magnesium Levels in Ischemic Rat Heart

Cited by 215 publications

References 30 publications

Model Study of ATP and ADP Buffering, Transport of Ca2+ and Mg2+,and Regulation of Ion Pumps in Ventricular Myocyte

Model Study of ATP and ADP Buffering, Transport of Ca2+ and Mg2+,and Regulation of Ion Pumps in Ventricular Myocyte

Simulation of Ca ²⁺ -activated Cl ⁻ current of cardiomyocytes in rabbit pulmonary vein: implications of subsarcolemmal Ca ²⁺ dynamics

A yeast with muscle doesn’t run faster: full humanization of the glycolytic pathway in Saccharomyces cerevisiae

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Cytosolic Free Magnesium Levels in Ischemic Rat Heart

Cited by 215 publications

References 30 publications

Model Study of ATP and ADP Buffering, Transport of Ca2+ and Mg2+,and Regulation of Ion Pumps in Ventricular Myocyte

Model Study of ATP and ADP Buffering, Transport of Ca2+ and Mg2+,and Regulation of Ion Pumps in Ventricular Myocyte

Simulation of Ca 2+ -activated Cl − current of cardiomyocytes in rabbit pulmonary vein: implications of subsarcolemmal Ca 2+ dynamics

A yeast with muscle doesn’t run faster: full humanization of the glycolytic pathway in Saccharomyces cerevisiae

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Simulation of Ca ²⁺ -activated Cl ⁻ current of cardiomyocytes in rabbit pulmonary vein: implications of subsarcolemmal Ca ²⁺ dynamics