Relationship between Calcium Transients and Myosin Cross-Bridge Kinetics at Different Lengths of the Atrial and Ventricular Myocardium in Control Rats and Rats with a Monocrotaline Model of Pulmonary Hypertension with Heart Failure

The effect of myocardial stretch on calcium kinetics in cardiomyocytes is manifested as a crossover in the superposition of calcium transient (CaT) curves at long and short lengths. CaT curves were recorded using Fura-2 AM in multicellular myocardial strips from the right heart of male Wistar rats in a control group (CONT) and in a group with monocrotaline-induced cardiopulmonary failure (MCT) in an intact state, during the slowing of myosin cross-bridge cycling with 1 µM omecamtiv mecarbil (OM), and during electromechanical uncoupling with 10 µM blebbistatin (BB). It was found that length-dependent, oppositely directed changes in different phases of the CaT decay are less pronounced in the right ventricular (RV) myocardium of the MCT group compared to the CONT group. In the right atrial (RA) myocardium of both groups, the crossover is weakly pronounced. In the ventricular myocardium, OM increases CaT crossover manifestation at different lengths in the early phase of the decay and decreases it in the late phase in the CONT group. In the MCT group, OM decreases CaT crossover manifestation in the RV myocardium in both phases. In the RA myocardium, OM increases CaT crossover manifestation upon myocardial stretch. BB causes the disappearance of CaT crossover in the RV myocardium of both groups. Length-dependent changes of CaT duration are monotonic under BB treatment. Based on the data obtained, we hypothesize that CAT crossover at different lengths in the RV myocardium results from changes in the number of myosin heads in a strongly actin-bound state and the cycling rate of myosin cross-bridges. Furthermore, CaT crossover is modulated by the rate of calcium ion removal from the sarcoplasm. The absence of length-dependent CaT changes in the RA myocardium of rats in both groups is likely due to a more powerful and developed calcium-sequestering system in the RA compared to the RV.