Morphological characteristics of cardiac calcium release units in animals with metabolic and circulatory disorders

Kelly F McGrath1, Atsumu Yuki, Yasutaka Manaka

  • 1Department of Physiological Sciences, National Institute of Fitness and Sports, Kanoya, Kagoshima, Japan. kellyfmcgrath@aim.com

Insights

Diabetic and hypertensive rat models show disrupted cardiac calcium release units (CRUs) and altered transverse-tubule orientation, potentially explaining cardiac dysfunction in these conditions.

Area of Science:

  • Cardiovascular Biology
  • Cellular Physiology
  • Molecular Cardiology

Background:

  • Metabolic and circulatory disorders, including diabetes and hypertension, are linked to cardiac dysfunction.
  • Abnormalities in cellular calcium handling, specifically calcium sparks and waves, are implicated in altering myocardial excitation-contraction coupling.
  • The precise spatial arrangement of the sarcolemma and sarcoplasmic reticulum calcium release units (CRUs) is critical for excitation-contraction coupling.

Purpose of the Study:

  • To investigate abnormalities in CRUs within the myocardium of type II diabetic and hypertensive rat models.
  • To assess the structural integrity and spatial organization of CRUs in the context of these metabolic and circulatory disorders.

Main Methods:

  • Myocardial tissue samples were obtained from diabetic and hypertensive rat models.
  • Tissue underwent perfusion fixation and selective staining of CRUs.
  • High-voltage electron microscopy was employed to observe CRU morphology and t-tubule organization.

Main Results:

  • Diabetic rat models exhibited increased body weight, a tendency towards cardiac enlargement, disrupted CRUs, and longitudinal displacement of transverse (t)-tubules.
  • Hypertensive rat models displayed significant cardiac enlargement, increased CRU disruption, and a tendency towards longitudinal t-tubule orientation.
  • Both models showed significant alterations in CRU structure and t-tubule architecture.

Conclusions:

  • Diabetes and hypertension share a potential common pathway in the etiology of cardiomyopathy, partly due to increased incomplete CRUs.
  • Morphological changes in the architecture and orientation of t-tubules contribute to CRU abnormalities.
  • These structural changes offer a potential explanation for impaired calcium signaling observed in diabetic and hypertensive cardiomyopathy.

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