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Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles
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Cholesterol is required for maintaining T-tubule integrity and intercellular connections at intercalated discs in

Yanqi Zhu1, Caimei Zhang2, Biyi Chen2

  • 1Department of Cardiology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China; Division of Cardiovascular Medicine, Department of Internal Medicine, François M. Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Journal of Molecular and Cellular Cardiology
|June 4, 2016
PubMed

Insights

Cholesterol depletion damages cardiac T-tubules and intercalated discs, impairing heart function. Restoring cholesterol levels can improve T-tubule structure and calcium handling in heart failure.

Area of Science:

  • Cardiovascular Biology
  • Cellular Physiology
  • Membrane Biophysics

Background:

  • Low serum cholesterol is linked to arrhythmias and poor prognosis in chronic heart failure.
  • Mechanisms connecting cholesterol levels to cardiac dysfunction are not fully understood.
  • Cardiac transverse (T)-tubule damage is implicated in excitation-contraction coupling dysfunction.

Purpose of the Study:

  • To investigate the role of membrane cholesterol in cardiac T-tubule structure and function.
  • To test the hypothesis that cholesterol depletion causes T-tubule remodeling and excitation-contraction coupling dysfunction.

Main Methods:

  • Isolated murine cardiomyocytes were treated with methyl-β-cyclodextrin (MβCD) to deplete cholesterol.
  • T-tubule integrity, calcium transients, and calcium release were analyzed.
  • Intact hearts were perfused with MβCD to assess effects on T-tubules and intercellular connections.

Main Results:

  • Cholesterol depletion progressively damaged T-tubule structure in a dose- and time-dependent manner.
  • MβCD treatment reduced calcium transient amplitude, increased calcium release dyssynchrony, and elevated spontaneous calcium sparks.
  • Cholesterol reintroduction partially restored T-tubule integrity and calcium handling.
  • In intact hearts, MβCD disrupted intercellular connections at intercalated discs.

Conclusions:

  • Cholesterol is essential for maintaining cardiac T-tubule structure.
  • Cholesterol depletion impairs cardiac excitation-contraction coupling by affecting T-tubules.
  • Cholesterol also plays a critical role in the integrity of intercalated discs between cardiomyocytes.
Abstract

Keywords:
Ca(2+) handlingCardiomyocytesCholesterolIntercalated discsT-tubules

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