Cardiomyocyte Ca2+ handling and structure is regulated by degree and duration of mechanical load variation

Journal of Cellular and Molecular Medicine

Michael Ibrahim¹  Punam Kukadia¹  Urszula Siedlecka¹  James E. Cartledge¹  Manoraj Navaratnarajah¹  Sergiy Tokar¹  Carin Van Doorn¹  Victor T. Tsang¹  Julia Gorelik¹  Magdi H. Yacoub¹ 

[1] Heart Science Centre, National Heart and Lung Institute, Imperial College London, London, UK

关键词: assist device;    Ca2+ handling;    excitation–contraction coupling;   

DOI  :  10.1111/j.1582-4934.2012.01611.x

来源: Wiley

【 摘 要 】

Abstract

Cardiac transverse (t)-tubules are altered during disease and may be regulated by stretch-sensitive molecules. The relationship between variations in the degree and duration of load and t-tubule structure remains unknown, as well as its implications for local Ca²⁺-induced Ca²⁺ release (CICR). Rat hearts were studied after 4 or 8 weeks of moderate mechanical unloading [using heterotopic abdominal heart–lung transplantation (HAHLT)] and 6 or 10 weeks of pressure overloading using thoracic aortic constriction. CICR, cell and t-tubule structure were assessed using confocal-microscopy, patch-clamping and scanning ion conductance microscopy. Moderate unloading was compared with severe unloading [using heart-only transplantation (HAHT)]. Mechanical unloading reduced cardiomyocyte volume in a time-dependent manner. Ca²⁺ release synchronicity was reduced at 8 weeks moderate unloading only. Ca²⁺ sparks increased in frequency and duration at 8 weeks of moderate unloading, which also induced t-tubule disorganization. Overloading increased cardiomyocyte volume and disrupted t-tubule morphology at 10 weeks but not 6 weeks. Moderate mechanical unloading for 4 weeks had milder effects compared with severe mechanical unloading (37% reduction in cell volume at 4 weeks compared to 56% reduction after severe mechanical unloading) and did not cause depression and delay of the Ca²⁺ transient, increased Ca²⁺ spark frequency or impaired t-tubule and cell surface structure. These data suggest that variations in chronic mechanical load influence local CICR and t-tubule structure in a time- and degree-dependent manner, and that physiological states of increased and reduced cell size, without pathological changes are possible.

【 授权许可】

Unknown   
© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd