Effect of Length-Dependent Changes in Myosin Cross-Bridge Kinetics on Calcium Transients in Right Atrial and Right Ventricular Myocardium of Rats

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 cross-bridge kinetics to CaT changes, length-dependent changes in CaT were assessed in three states of myosin cross-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 cross-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.