Although coupling between cardiomyocytes and myofibroblasts is well known to affect the physiology and pathophysiology of cardiac tissues across species, relating these observations to humans is challenging because the effect of this coupling varies across species and because the sources of these effects are not known. To identify the sources of cross-species variation, we built upon previous mathematical models of myofibroblast electrophysiology and developed a mechanoelectrical model of cardiomyocyte-myofibroblast interactions as mediated by electrotonic coupling and transforming growth factor-β1. The model, as verified by experimental data from the literature, predicted that both electrotonic coupling and transforming growth factor-β1 interaction between myocytes and myofibroblast prolonged action potential in rat myocytes but shortened action potential in human myocytes. This variance could be explained by differences in the transient outward K⁺ current associated with differential Kv4.2 gene expression across species. Results are useful for efforts to extrapolate the results of animal models to the predicted effects in humans and point to potential therapeutic targets for fibrotic cardiomyopathy.

尽管众所周知，心肌细胞和肌成纤维细胞之间的耦合会影响跨物种心脏组织的生理学和病理生理学，但将这些观察结果与人类联系起来具有挑战性，因为这种耦合的影响因物种而异，而且这些影响的来源尚不清楚。为了确定跨物种变异的来源，我们建立在先前的肌成纤维细胞电生理数学模型的基础上，并开发了一种由电耦合和转化生长因子-β1介导的心肌细胞-肌成纤维细胞相互作用的机械电模型。该模型已通过实验数据验证从文献中预测，电渗耦合和转化生长因子-β1 肌细胞和肌成纤维细胞之间的相互作用延长了大鼠肌细胞的动作电位，但缩短了人肌细胞的动作电位。这种差异可以通过与物种间差异 Kv4.2 基因表达相关的瞬时外向 K ^{+电流的差异来解释。}结果有助于将动物模型的结果外推到对人类的预测效果，并指出纤维化心肌病的潜在治疗靶点。