Cardiac muscle regulatory units are predicted to interact stronger than neighboring cross-bridges

Kalda, Mari; Vendelin, Marko

doi:10.1038/s41598-020-62452-7

Cited by 2 publications

(1 citation statement)

References 41 publications

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“…Compared with murine α-MyHC, human and porcine β-MyHCs exhibit a nearly 10-fold slower rate of ADP release ( Deacon et al, 2012 ; Walklate et al, 2016 , 2021 ), which could prolong the occupancy of β-MyHC bound to actin and thereby contribute to the cooperative recruitment of cross-bridges and activation of steady-state force. In the healthy porcine and human ventricular myocardium, we propose that the expression of a small amount of fast α-MyHC on a predominantly slow β-MyHC background in combination with strong near-neighbor regulatory unit (RU) interactions ( Razumova et al, 2000 ; Kalda and Vendelin, 2020 ) provides the predominant molecular mechanisms underlying thin filament activation. Following Ca 2+ binding to TnC, we propose that α-MyHC is the first to bind to the thin filament and because of its activating effects, α-MyHC opens the thin filament for initial β-MyHC binding and the subsequent cooperative spread of β-MyHC binding.…”

Section: Discussionmentioning

confidence: 99%

Cooperative mechanisms underlie differences in myocardial contractile dynamics between large and small mammals

Patel,

Park,

Bradshaw

et al. 2023

Journal of General Physiology

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Ca2+ binding to troponin C (TnC) and myosin cross-bridge binding to actin act in a synergistic cooperative manner to modulate myocardial contraction and relaxation. The responsiveness of the myocardial thin filament to the activating effects of Ca2+ and myosin cross-bridge binding has been well-characterized in small mammals (e.g., mice). Given the nearly 10-fold difference in resting heart rates and twitch kinetics between small and large mammals, it is unlikely that the cooperative mechanisms underlying thin filament activation are identical in these two species. To test this idea, we measured the Ca2+ dependencies of steady-state force and the rate constant of force redevelopment (ktr) in murine and porcine permeabilized ventricular myocardium. While murine myocardium exhibited a steep activation-dependence of ktr, the activation-dependent profile of ktr was significantly reduced in porcine ventricular myocardium. Further insight was attained by examining force–pCa and ktr–pCa relationships. In the murine myocardium, the pCa50 for ktr was right-shifted compared with the pCa50 for force, meaning that increases in steady-state force occurred well before increases in the rate of force redevelopment were observed. In the porcine myocardium, we observed a tighter coupling of the force–pCa and ktr–pCa relationships, as evidenced by near-maximal rates of force redevelopment at low levels of Ca2+ activation. These results demonstrate that the molecular mechanisms underlying the cooperative activation of force are a dynamic property of the mammalian heart, involving, at least in part, the species- and tissue-specific expression of cardiac myosin heavy chain isoforms.

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