Transient K + current explains cross-species differences in the effects of myofibroblasts on myocytes
Transient K + current explains cross-species differences in the effects of myofibroblasts on myocytes
Abstract Electrical and paracrine couplings between cardiomyocytes (CMs) and myofibroblasts (MFBs) affect both physiology and pathophysiology of cardiac tissues in a range of animal models, but relating these observations to humans is a challenge because effects vary greatly across species. To address this challenge, we developed a mathematical model for mechanoelectrical interactions between CM and MFB, considering both electrical and paracrine couplings between CMs and MFBs, with the aim of identifying the sources of cross-species variation and extrapolating animal models to predicted effects in humans. Our results revealed substantial differences across species in how these couplings modulate excitation-contraction coupling and Ca2+ transients of CMs. Both classes of couplings prolong action potential and increase APD in rat CMs, but shorten action potential and decrease APD in human CMs. Electrical coupling attenuates Ca2+ transients and active tension generation in human CMs, but has no significant effect on rat CMs. Paracrine coupling reduces Ca2+ transients and active tension in both human and rat CM. The results suggest that the variance of functional interactions between CM and MFB in cross-species may be explained by differences in the transient outward K+ currents associated with the KCND2 gene, and thus suggest potential therapeutic pathways for fibrotic cardiomyopathy.
Wu Hou、Dong Yuqin、Xu Feng、Huang Guoyou、Liu Fusheng、Lu Tian Jian、Genin Guy M.、Yang Xiaoyu
State Key Laboratory for Strength and Vibration of Mechanical Structures, Xi?ˉan Jiaotong University||Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi?ˉan Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi?ˉan Jiaotong University||Bioinspired Engineering and Biomechanics Center (BEBC), Xi?ˉan Jiaotong UniversityKey Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi?ˉan Jiaotong University||Bioinspired Engineering and Biomechanics Center (BEBC), Xi?ˉan Jiaotong UniversityDepartment of Engineering Mechanics, School of Civil Engineering, Wuhan UniversityState Key Laboratory for Strength and Vibration of Mechanical Structures, Xi?ˉan Jiaotong University||Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi?ˉan Jiaotong University||Bioinspired Engineering and Biomechanics Center (BEBC), Xi?ˉan Jiaotong UniversityState Key Laboratory of Mechanics and Control of Mechanical Structures, Nanjing University of Aeronautics and AstronauticsKey Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi?ˉan Jiaotong University||Bioinspired Engineering and Biomechanics Center (BEBC), Xi?ˉan Jiaotong University||Department of Mechanical Engineering & Materials Science, Washington University in St. Louis||NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. LouisState Key Laboratory for Strength and Vibration of Mechanical Structures, Xi?ˉan Jiaotong University||Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi?ˉan Jiaotong University
基础医学生理学分子生物学
Myocardial fibrosisElectrical couplingParacrine communicationExcitation-contraction coupling
Wu Hou,Dong Yuqin,Xu Feng,Huang Guoyou,Liu Fusheng,Lu Tian Jian,Genin Guy M.,Yang Xiaoyu.Transient K + current explains cross-species differences in the effects of myofibroblasts on myocytes[EB/OL].(2025-03-28)[2025-05-18].https://www.biorxiv.org/content/10.1101/2020.11.02.365650.点此复制
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