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Investigations of Molecular Mechanisms of Actin–Myosin Interactions in Cardiac Muscle

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Abstract

The functional characteristics of cardiac muscle depend on the composition of protein isoforms in the cardiomyocyte contractile machinery. In the ventricular myocardium of mammals, several isoforms of contractile and regulatory proteins are expressed–two isoforms of myosin (V1 and V3) and three isoforms of tropomyosin chains (α, β, and κ). Expression of protein isoforms depends on the animal species, its age and hormonal status, and this can change with pathologies of the myocardium. Mutations in these proteins can lead to cardiomyopathies. The functional significance of the protein isoform composition has been studied mainly on intact hearts or on isolated preparations of myocardium, which could not provide a clear comprehension of the role of each particular isoform. Present-day experimental techniques such as an optical trap and in vitro motility assay make it possible to investigate the phenomena of interactions of contractile and regulatory proteins on the molecular level, thus avoiding effects associated with properties of a whole muscle or muscle tissue. These methods enable free combining of the isoforms to test the molecular mechanisms of their participation in the actin–myosin interaction. Using the optical trap and the in vitro motility assay, we have studied functional characteristics of the cardiac myosin isoforms, molecular mechanisms of the calcium-dependent regulation of actin–myosin interaction, and the role of myosin and tropomyosin isoforms in the cooperativity mechanisms in myocardium. The knowledge of molecular mechanisms underlying myocardial contractility and its regulation is necessary for comprehension of cardiac muscle functioning, its disorders in pathologies, and for development of approaches for their correction.

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Abbreviations

AOD:

acousto-optical deflector

A7TmTn:

a regulatory group consisting of seven G-actin molecules, one tropomyosin molecule, and one troponin molecule

CaTnC:

calcium–troponin complex

CaTnC–CaTnC:

troponin–troponin cooperativity

F-actin:

filamentary actin

G-actin:

globular actin

HMM:

heavy meromyosin

LMM:

light meromyosin

MHC:

myosin heavy chains

NEM:

N-ethylmaleimide

pCa:

negative decimal logarithm of calcium concentration

pCa50 :

the calcium concentration corresponding to half-maximum of the sliding velocity or of the force (calcium sensitivity)

S1:

subfragment 1, or myosin molecule head

S2:

subfragment 2, or rod of heavy meromyosin

Tm:

tropomyosin

TnC:

troponin C

TnI:

troponin I

TnT:

troponin T

V max :

maximal velocity of muscle shortening

Xb:

cross-bridge

Xb–CaTnC:

bridge–troponin cooperativity.

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Authors and Affiliations

  1. Institute of Immunology and Physiology, Ural Division of the Russian Academy of Sciences, 620041, Ekaterinburg, Russia

    L. V. Nikitina, G. V. Kopylova, D. V. Shchepkin, S. R. Nabiev & S. Y. Bershitsky

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  1. L. V. Nikitina
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  2. G. V. Kopylova
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Original Russian Text © L. V. Nikitina, G. V. Kopylova, D. V. Shchepkin, S. R. Nabiev, S. Y. Bershitsky, 2015, published in Uspekhi Biologicheskoi Khimii, 2015, Vol. 55, pp. 255-288.

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Nikitina, L.V., Kopylova, G.V., Shchepkin, D.V. et al. Investigations of Molecular Mechanisms of Actin–Myosin Interactions in Cardiac Muscle. Biochemistry Moscow 80, 1748–1763 (2015). https://doi.org/10.1134/S0006297915130106

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