The lack of slow force response in failing rat myocardium: role of stretch-induced modulation of Ca–TnC kinetics
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The slow force response (SFR) to stretch is an important adaptive mechanism of the heart. The SFR may result in ~ 20–30% extra force but it is substantially attenuated in heart failure. We investigated the relation of SFR magnitude with Ca2+ transient decay in healthy (CONT) and monocrotaline-treated rats with heart failure (MCT). Right ventricular trabeculae were stretched from 85 to 95% of optimal length and held stretched for 10 min at 30 °C and 1 Hz. Isometric twitches and Ca2+ transients were collected on 2, 4, 6, 8, 10 min after stretch. The changes in peak tension and Ca2+ transient decay characteristics during SFR were evaluated as a percentage of the value measured immediately after stretch. The amount of Ca2+ utilized by TnC was indirectly evaluated using the methods of Ca2+ transient “bump” and “difference curve.” The muscles of CONT rats produced positive SFR and they showed prominent functional relation between SFR magnitude and the magnitude (amplitude, integral intensity) of Ca2+ transient “bump” and “difference curve.” The myocardium of MCT rats showed negative SFR to stretch (force decreased in time) which was not correlated well with the characteristics of Ca2+ transient decay, evaluated by the methods of “bump” and “difference curve.” We conclude that the intracellular mechanisms of Ca2+ balancing during stretch-induced slow adaptation of myocardial contractility are disrupted in failing rat myocardium. The potential significance of our findings is that the deficiency of slow force response in diseased myocardium may be diminished under augmented kinetics of Ca–TnC interaction.
KeywordsSlow force response Rat myocardium Heart failure Isometric contraction Ca2+ transient
The authors thank Daniil Kuznetsov for his help in the implementation of the monocrotaline-based experimental model of pulmonary hypertension in rats.
The study was carried out within the framework of the IIF UrB RAS theme No AAAA-A18-118020590031-8, supported by RFBR (grants #16-04-00545 and #18-04-00572), by the Program of the Ural Branch of RAS (No. 18-7-4-15, AAAA-A18-118020590134-6) and by RF Government Act #211 of March 16, 2013 (agreement 02.A03.21.0006).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing financial interests.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the local institutional ethics committee.
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