Study of the influence of long-dependent changes in myosin bridge kinetics on calcium transient in the myocardium of the right atrium and right ventricle of rats

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Аннотация

Heterometric regulation of myocardial contractility is the most important property regulating the pumping function of the heart. Calcium ions play a key role in the activation and regulation of muscle contraction. In addition to changes in the degree of actin-myosin filament overlap, one consequence of myocardial stretch is a length-dependent change in the shape and duration of the intracellular calcium transient (CaT). As the degree of myocardial stretch increases, the duration of the CaT decreases in the upper half of the CaT decline and increases in the lower half. To determine the contribution of myosin bridge kinetics to CaT changes, length-dependent changes in CaT were assessed in three states of myosin bridge kinetics; (1) intact, (2) slowed under the influence of omecamtiv mecarbil 1 µM (OM), and (3) blocked under the influence of blebbistatin 10 µM (BB). It was found that length-dependent multidirectional changes in CaT decay (CaT crossover phenomenon) were pronounced in the right ventricular (RV) myocardium and weak in the right atrial (RA) myocardium of intact male nine-week-old Wistar rats. OM significantly slows the rate of tension development and decline in myocardium of RA and RV rats; enhances length-dependent changes in CaT duration; OM decreases the duration of CaT at 80% of its amplitude and increases the duration of CaT at 20% of its amplitude in both RA and RV. BB almost completely abolishes the ability of the myocardium to develop tension; length-dependent changes in CaT duration are monotonous, CaT crossover in RV myocardium disappears. The phenomenon of CaT crossover in the myocardium of the RV is a consequence of the attachment and detachment of myosin bridges to the thin filament. The absence of length-dependent changes in CaT in rat RA myocardium seems to be associated with a more developed calcium sequestering system in RA, in comparison with the calcium sequestering system in RV.

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Авторлар туралы

R. Lisin

Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences

Хат алмасуға жауапты Автор.
Email: lisin.ruslan@gmail.com
Ресей, Yekaterinburg

A. Balakin

Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences

Email: lisin.ruslan@gmail.com
Ресей, Yekaterinburg

A. Zudova

Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences

Email: lisin.ruslan@gmail.com
Ресей, Yekaterinburg

Yu. Protsenko

Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences

Email: lisin.ruslan@gmail.com
Ресей, Yekaterinburg

Әдебиет тізімі

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2. Fig. 1. Representative examples of changes in the time course of mechanical stress (a and b) and the CaT glow signal (c and d) in a single contraction-relaxation cycle in response to a change in the initial length of the rat right ventricle (RV) and right atrium (RA) strip in Krebs–Henseleit solution. Stimulation frequency was 2 Hz and temperature was 30°C. CaT were normalized to their own amplitude. The relative lengths of the muscle preparations are shown in panel (a).

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3. Fig. 2. Representative trajectories of mechanical stress (a and b) and the corresponding CaT (c and d) in single isometric contractions of the right atrium (RA) and right ventricle (RV) preparations at the length Lmax in Krebs–Henseleit (blue), omecamtiv mecarbil 1 μM (red), and blebbistatin 10 μM (green) solutions. Stimulation frequency 2 Hz, temperature 30ºС. r.u. – relative units.

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4. Fig. 3. Dependence of the active mechanical tension on the length (preload) of the myocardial strips of the right atrium (a) and right ventricle (b) of rats in a solution of Krebs–Henseleit (blue), omecamtiv mecarbil 1 μM (red) and blebbistatin 10 μM (green). Stimulation frequency 2 Hz, temperature 30ºС. * – p < 0.01, Friedman ANOVA, the effect of the solution factor (the effect of omecamtiv mecarbil 1 μM and blebbistatin 10 μM) on the active tension at a specific preload. The data are presented as scatter plots with superimposed box plots, where Q1 is the lower boundary of the box, Q3 is the upper boundary of the box, the median is the horizontal line inside the box, the whiskers of the box are the minimum and maximum values, and the points outside the whiskers are outliers.

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5. Fig. 4. Dependence of the normalized value of the maximum rate of development (a and b) and relaxation of mechanical stress (c and d) on the length (preload) of the myocardial strips of the right atrium RA (a, c) and right ventricle RV (b, d) of rats in Krebs–Henseleit solution (blue), omecamtiv mecarbil 1 μM (red). Stimulation frequency is 2 Hz, solution temperature is 30ºС. The data are presented as scatterplots with superimposed boxplots, where Q1 is the lower boundary of the box, Q3 is the upper boundary of the box, the median is the horizontal line inside the box, the whiskers are the minimum and maximum values, and points outside the whiskers are outliers. * – p < 0.01, Wilcoxon test, effect of OM on ((dP/dt)/Pmax )max at a given preload.

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6. Fig. 5. Superposition of representative calcium transient (CaT) curves in Krebs–Henseleit solution (a and b); solution containing 1 μM omecamtiv mecarbil (c and d); and a solution containing 10 μM blebbistatin (e and f) on different lengths of the myocardium of the right atrium RA (a, c, e) and right ventricle RV (b, d, f) of the hearts of intact rats. The length values and the corresponding color are given in the legend. The stimulation frequency was 2 Hz, the solution temperature was 30 °C. Panel (b) shows the scheme for calculating T dur 20 and T dur 80 of the duration of CaT at the level of 20% and 80% of its amplitude. The arrows in panel (d) indicate the shift of the CaT signal with an increase in the degree of stretching of the RV trabecula relative to the CaT signal at the shortest muscle length, r.u. are relative units.

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7. Fig. 6. Dependence of the value of T dur 20 CaT and T dur 80 CaT (duration of CaT at the level of 20 and 80%) on the length of the myocardial strips of the right atrium (a and c) and right ventricle (b and d) of rats in the Krebs–Henseleit solution (blue), in a solution containing 1 μM omecamtiv mecarbil (red), and in a solution containing 10 μM blebbistatin (green). The stimulation frequency was 2 Hz, the solution temperature was 30 °C. The data are presented as scatter plots with superimposed box plots, where Q1 is the lower boundary of the box, Q3 is the upper boundary of the box, the median is the horizontal line inside the box, the whiskers of the box are the minimum and maximum values, and the points outside the whiskers are outliers. # – p < 0.01, Friedman ANOVA, factor – muscle length; * – p < 0.05, Friedman ANOVA, factor – effect of OM and BB solutions.

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8. Fig. 7. Effect of muscle length and cross-bridge cycling rate on CaT. Graphical scheme of the experiment and the results obtained for the RV trabeculae.

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