Cardiomyocyte substructure reverts to an immature phenotype during heart failure

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp13430-list-0001">As reactivation of the fetal gene program has been implicated in pathological remodelling during heart failure (HF), we examined whether cardiomyocyte subcellular structure and function revert to an immature phenotype during this disease.Surface and internal membrane structures appeared gradually during development, and returned to a juvenile state during HF. Similarly, dyadic junctions between the cell membrane and sarcoplasmic reticulum were progressively ‘packed’ with L‐type Ca²⁺ channels and ryanodine receptors during development, and ‘unpacked’ during HF.Despite similarities in subcellular structure, dyads were observed to be functional from early developmental stages, but exhibited an impaired ability to release Ca²⁺ in failing cardiomyocytes.Thus, while immature and failing cardiomyocytes share similarities in subcellular structure, these do not fully account for the marked impairment of Ca²⁺ homeostasis observed in HF.