Role of t-tubule remodeling on mechanisms of abnormal calcium release during heart failure development in canine ventricle

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Abstract
Three-dimensional analysis of t-tubule density showed t-tubule disruption throughout the whole myocyte in failing dog ventricle. A double-linear relationship between Ca2+ release and t-tubule density displays a steeper slope at t-tubule densities below a threshold value (∼1.5%) above which there is little effect on Ca2+ release (T-tubule reserve). T-tubule loss increases incidence of triggered Ca2+ waves. Chemically induced t-tubule disruption suggests that t-tubule loss alone is a critical component of abnormal Ca2+ cycling in heart failure.
Funding Information
  • HHS | NIH | National Heart, Lung, and Blood Institute (R01HL125881)
  • HHS | NIH | National Heart, Lung, and Blood Institute (R01HL140061)
  • HHS | NIH | National Heart, Lung, and Blood Institute (R01 HL107577)
  • HHS | NIH | National Heart, Lung, and Blood Institute (R01 HL127028)
  • HHS | NIH | National Heart, Lung, and Blood Institute (R01 HL140731)
  • HHS | NIH | National Heart, Lung, and Blood Institute (R01 HL149423)
  • HHS | NIH | National Heart, Lung, and Blood Institute (R01 HL119095)
  • American Heart Association (16SFRN28780016)
  • HHS | NIH | National Heart, Lung, and Blood Institute (R01 HL119095)

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