Calcium Bump as Indicator of the Mechano-Calcium Feedback in Cardiomyocytes and its Species-specificity in Mathematical Models

Pavel Konovalov1, Nathalie Balakina-Vikulova2, Olga Solovyova1, Leonid Katsnelson3
1Institute of Immunology and Physiology of the RAS, 2Ural Federal University, 3Institute of Immunology and Physiology of the RAS at Ekaterinburg


Mechano-calcium feedback mechanisms manifest themselves as a number of experimental effects including a visible bending of the phase of the calcium transient decay ("calcium bump"). It has been experimentally established that the bump intensity depends on the mechanical conditions of the myocardium contractions, e.g. on the preload, i.e. on the cardiomyocyte initial lengthening (Jiang et al, Am. J. Physiol., 1998). Moreover, McDonald et al (Biochem. Res. Int., 2012) showed that the extent of the bump could be species-specific. In particular, in the absolute majority of cases, Ca2+ transients in the porcine cardiomyocytes revealed significant bumps. The authors emphasized that the pig was chosen due to the morphological and functional similarity of its heart to the human. In contrast to porcine Ca2+ transients, the bumps did not arise in their experiments in the mice cardiomyocytes. Here, we compare simulations obtained in our mathematical models of the excitation-contraction coupling in human cardiomyocytes (Balakina-Vikulova et al, J. Physiol. Sci., 2020) and in mouse cardiomyocytes (Khokhlova et al, Front. Physiol. 2020). According to the predictions of the models, the bump is characteristic of human cardiomyocytes at any initial lengths, but in mouse the bump manifests itself clearly only at the initial lengths of 0.95 Lmax or bigger and completely disappears at 0.85 Lmax and smaller. These simulations correlate well with the data of McDonald ea. Mice are one of the most common laboratory models for analyzing and predicting physiological mechanisms characteristic of warm-blooded animals, including humans. Obviously, such predictions should be made with great limitations. Our particular results indicate this once more.