Danicamtiv affected isometric force and cross-bridge kinetics similarly in skinned myocardial strips from male and female rats.

Autor: Awinda PO; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, 99164, USA., Vander Top BJ; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, 99164, USA., Turner KL; School of Molecular Biosciences, Washington State University, Pullman, WA, 99164, USA., Tanner BCW; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, 99164, USA. bertrand.tanner@wsu.edu.; Department of Integrative Physiology and Neuroscience, Washington State University, Room 255 Vet/Biomed Research Building, 1815 Ferdinand's Lane, Pullman, WA, 99164-7620, USA. bertrand.tanner@wsu.edu.
Jazyk: angličtina
Zdroj: Journal of muscle research and cell motility [J Muscle Res Cell Motil] 2024 Sep; Vol. 45 (3), pp. 115-122. Date of Electronic Publication: 2024 May 08.
DOI: 10.1007/s10974-024-09669-5
Abstrakt: Myotropes are pharmaceuticals that have recently been developed or are under investigation for the treatment of heart diseases. Myotropes have had varied success in clinical trials. Initial research into myotropes have widely focused on animal models of cardiac dysfunction in comparison with normal animal cardiac physiology-primarily using males. In this study we examined the effect of danicamtiv, which is one type of myotrope within the class of myosin activators, on contractile function in permeabilized (skinned) myocardial strips from male and female Sprague-Dawley rats. We found that danicamtiv increased steady-state isometric force production at sub-maximal calcium levels, leading to greater Ca 2+ -sensitivity of contraction for both sexes. Danicamtiv did not affect maximal Ca 2+ -activated force for either sex. Sinusoidal length-perturbation analysis was used to assess viscoelastic myocardial stiffness and cross-bridge cycling kinetics. Data from these measurements did not vary with sex, and the data suggest that danicamtiv slows cross-bridge cycling kinetics. These findings imply that danicamtiv increases force production via increasing cross-bridge contributions to activation of contraction, especially at sub-maximal Ca 2+ -activation. The inclusion of both sexes in animal models during the formative stages of drug development could be helpful for understanding the efficacy or limitation of a drug's therapeutic impact on cardiac function.
(© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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