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Distribution of calcium in a subset of chronic hibernating myocardium in man
M Borgers1, S De Nollin, F Thoné
1Department of Morphology, Life Sciences, Janssen Research Foundation, Beerse, Belgium.
Insights
Chronic hibernating myocardium involves myocardial cells with reduced contractile material and increased glycogen. Calcium accumulates in affected cells, suggesting preserved calcium homeostasis and ruling out ischemia.
Area of Science:
- Cardiology
- Cell Biology
- Biochemistry
Background:
- Chronic hibernating myocardium is characterized by structural changes in myocardial cells, shifting from a functional to a survival state.
- These cells exhibit reduced contractile material and increased glycogen stores.
- Previous studies noted structural alterations in calcium-handling organelles like the sarcoplasmic reticulum (SR), sarcolemma, and mitochondria.
Purpose of the Study:
- To investigate the subcellular distribution of calcium in myocardial cells affected by chronic hibernating myocardium.
- To determine if calcium dysregulation contributes to the 'hibernating' state.
- To assess the potential for preserved calcium homeostasis in these cells.
Main Methods:
- Biopsies from 'hibernating' myocardial regions were analyzed.
- Total calcium distribution was mapped using laser microprobe mass analysis (LAMMA).
- Exchangeable calcium was localized using the phosphate-pyroantimonate precipitation (PPA) method.
Main Results:
- LAMMA revealed significantly higher total calcium in glycogen-rich areas (myolytic areas) compared to mitochondria or sarcomeres.
- PPA showed calcium precipitate primarily at the sarcolemma, with minimal presence in mitochondria.
- Affected cells displayed a distinct calcium distribution pattern, with accumulation in myolytic areas and sarcolemmal retention.
Conclusions:
- The observed calcium distribution suggests a pool of bound calcium within the myolytic areas.
- Retention of calcium at the sarcolemma and absence in mitochondria indicate that these 'hibernating' cells may not be ischemic.
- These findings support the hypothesis that structurally affected myocardial cells retain the capacity to regulate their calcium homeostasis.
Abstract:
The structural correlates of 'chronic hibernating myocardium' in man consist of myocardial cells which transformed from a functional state (rich in contractile material) to a surviving state (poor in contractile material, rich in glycogen). Since the calcium-handling organelles such as SR, sarcolemma and mitochondria underwent structural changes in cells so affected, the distribution of calcium was investigated in biopsies obtained from 'hibernating' areas. The material was processed for microscopic localization of total calcium (laser microprobe mass analysis, LAMMA) and of exchangeable calcium (phosphate-pyroantimonate precipitation method, PPA). Subcellular distribution of total calcium as assessed by LAMMA revealed that in the structurally affected cells the areas in which sarcomeres were replaced by glycogen contained significantly more calcium than all other areas probed such as mitochondria, remaining sarcomeres at the cell periphery and subcellular areas of normally structured cells. Calcium precipitate, obtained after PPA assessment, was localized at the sarcolemma but was virtually absent in the mitochondria of affected cells. The high calcium content in the myolytic areas of affected cells most probably belongs to a pool of bound calcium. The observations that calcium is retained at the sarcolemma and that mitochondria are devoid of precipitate favour the hypothesis that cells structurally affected as such are not ischaemic and are still able to regulate their calcium homeostasis.