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Your search keyword '"Michailova, Anushka"' showing total 18 results
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18 results on '"Michailova, Anushka"'

1. Molecular and Subcellular-Scale Modeling of Nucleotide Diffusion in the Cardiac Myofilament Lattice

Author

Kekenes-Huskey, Peter M, Liao, Tao, Gillette, Andrew K, Hake, Johan E, Zhang, Yongjie, Michailova, Anushka P, McCulloch, Andrew D, and McCammon, J Andrew

Subjects
Biochemistry and Cell Biology, Biological Sciences, Heart Disease, Cardiovascular, Adenosine Diphosphate, Adenosine Triphosphatases, Adenosine Triphosphate, Anisotropy, Diffusion, Hydrolysis, Intracellular Space, Mitochondria, Models, Molecular, Molecular Conformation, Myofibrils, Nucleotides, Reproducibility of Results, Sarcomeres, Physical Sciences, Chemical Sciences, Biophysics, Biological sciences, Chemical sciences, Physical sciences
Abstract

Contractile function of cardiac cells is driven by the sliding displacement of myofilaments powered by the cycling myosin crossbridges. Critical to this process is the availability of ATP, which myosin hydrolyzes during the cross-bridge cycle. The diffusion of adenine nucleotides through the myofilament lattice has been shown to be anisotropic, with slower radial diffusion perpendicular to the filament axis relative to parallel, and is attributed to the periodic hexagonal arrangement of the thin (actin) and thick (myosin) filaments. We investigated whether atomistic-resolution details of myofilament proteins can refine coarse-grain estimates of diffusional anisotropy for adenine nucleotides in the cardiac myofibril, using homogenization theory and atomistic thin filament models from the Protein Data Bank. Our results demonstrate considerable anisotropy in ATP and ADP diffusion constants that is consistent with experimental measurements and dependent on lattice spacing and myofilament overlap. A reaction-diffusion model of the half-sarcomere further suggests that diffusional anisotropy may lead to modest adenine nucleotide gradients in the myoplasm under physiological conditions.

Published
2013

2. Modeling regulation of cardiac KATP and L-type Ca2+ currents by ATP, ADP, and Mg2+

Author

Michailova, Anushka, Saucerman, Jeffrey, Belik, Mary Ellen, and McCulloch, Andrew D

Subjects
Life Sciences (General)
Abstract

Changes in cytosolic free Mg(2+) and adenosine nucleotide phosphates affect cardiac excitability and contractility. To investigate how modulation by Mg(2+), ATP, and ADP of K(ATP) and L-type Ca(2+) channels influences excitation-contraction coupling, we incorporated equations for intracellular ATP and MgADP regulation of the K(ATP) current and MgATP regulation of the L-type Ca(2+) current in an ionic-metabolic model of the canine ventricular myocyte. The new model: 1), quantitatively reproduces a dose-response relationship for the effects of changes in ATP on K(ATP) current, 2), simulates effects of ADP in modulating ATP sensitivity of K(ATP) channel, 3), predicts activation of Ca(2+) current during rapid increase in MgATP, and 4), demonstrates that decreased ATP/ADP ratio with normal total Mg(2+) or increased free Mg(2+) with normal ATP and ADP activate K(ATP) current, shorten action potential, and alter ionic currents and intracellular Ca(2+) signals. The model predictions are in agreement with experimental data measured under normal and a variety of pathological conditions.

Published
2005
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13. Modeling Regulation of Cardiac KATPand L-type Ca2+Currents by ATP, ADP, and Mg2+

Author

Michailova, Anushka, Saucerman, Jeffrey, Ellen Belik, Mary, and McCulloch, Andrew D.

Abstract

Changes in cytosolic free Mg2+and adenosine nucleotide phosphates affect cardiac excitability and contractility. To investigate how modulation by Mg2+, ATP, and ADP of KATPand L-type Ca2+channels influences excitation-contraction coupling, we incorporated equations for intracellular ATP and MgADP regulation of the KATPcurrent and MgATP regulation of the L-type Ca2+current in an ionic-metabolic model of the canine ventricular myocyte. The new model: 1), quantitatively reproduces a dose-response relationship for the effects of changes in ATP on KATPcurrent, 2), simulates effects of ADP in modulating ATP sensitivity of KATPchannel, 3), predicts activation of Ca2+current during rapid increase in MgATP, and 4), demonstrates that decreased ATP/ADP ratio with normal total Mg2+or increased free Mg2+with normal ATP and ADP activate KATPcurrent, shorten action potential, and alter ionic currents and intracellular Ca2+signals. The model predictions are in agreement with experimental data measured under normal and a variety of pathological conditions.

Published
2005
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14. Spatiotemporal Features of Ca2+Buffering and Diffusion in Atrial Cardiac Myocytes with Inhibited Sarcoplasmic Reticulum

Author

Michailova, Anushka, DelPrincipe, Franco, Egger, Marcel, and Niggli, Ernst

Abstract

Ca2+signaling in cells is largely governed by Ca2+diffusion and Ca2+binding to mobile and stationary Ca2+buffers, including organelles. To examine Ca2+signaling in cardiac atrial myocytes, a mathematical model of Ca2+diffusion was developed which represents several subcellular compartments, including a subsarcolemmal space with restricted diffusion, a myofilament space, and the cytosol. The model was used to quantitatively simulate experimental Ca2+signals in terms of amplitude, time course, and spatial features. For experimental reference data, L-type Ca2+currents were recorded from atrial cells with the whole-cell voltage-clamp technique. Ca2+signals were simultaneously imaged with the fluorescent Ca2+indicator Fluo-3 and a laser-scanning confocal microscope. The simulations indicate that in atrial myocytes lacking T-tubules, Ca2+movement from the cell membrane to the center of the cells relies strongly on the presence of mobile Ca2+buffers, particularly when the sarcoplasmic reticulum is inhibited pharmacologically. Furthermore, during the influx of Ca2+large and steep concentration gradients are predicted between the cytosol and the submicroscopically narrow subsarcolemmal space. In addition, the computations revealed that, despite its low Ca2+affinity, ATP acts as a significant buffer and carrier for Ca2+, even at the modest elevations of [Ca2+]ireached during influx of Ca2+.

Published
2002
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