Morphological characteristics of cardiac calcium release units in animals with metabolic and circulatory disorders
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Published on: April 21, 2014
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.
Abstract:
Metabolic and circulatory disorders such as diabetes and hypertension are associated with cardiac dysfunction. Research on these types of experimental animals has observed abnormal calcium (Ca(2+)) sparks and waves in cells; a potential mechanism altering excitation-contraction (e-c) coupling in the myocardium. The e-c coupling depends on the intricate spatial relationship between the sarcolemma and sarcoplasmic reticulum calcium release units (CRU's). The objective of this study was to assess for a presence or absence of abnormalities in CRU's from type II diabetic and hypertensive rat models. Myocardial tissue underwent perfusion fixation followed by selective staining of the CRU's and the features observed using a high voltage electron microscope. Results revealed both diabetic groups had significant increases in body weight, a tendency toward an enlarged heart, and a significant disruption of the CRU's and displacement of transverse (t)-tubules in a longitudinal direction. The hypertensive model characteristically showed a dramatic increase in heart size, a significant increase in disrupted CRU's and a tendency towards longitudinal t-tubule orientation. We propose the two disorders of diabetes and hypertension have a similar etiology of cardiomyopathy resulting, in part, from an increase in the number of incomplete CRU's, due to a morphological change in the architecture and orientation of the t-tubules. These architectural changes could potentially explain the impaired calcium signaling previously observed in diabetic and hypertensive cardiomyopathy.
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