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

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 (Ca²⁺) 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.