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Defective excitation-contraction coupling in experimental cardiac hypertrophy and heart failure
A M Gómez1, H H Valdivia, H Cheng
1Department of Physiology and the Medical Biotechnology Center, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA. Universit.
Insights
High blood pressure causes cardiac hypertrophy and heart failure by impairing excitation-contraction coupling in heart cells. This defect reduces calcium release, leading to heart dysfunction, especially when compensatory mechanisms fail.
Area of Science:
- Cardiovascular Physiology
- Cellular Biology
- Pathophysiology
Background:
- Hypertension can lead to cardiac hypertrophy and heart failure.
- Excitation-contraction (EC) coupling is crucial for cardiac function.
- Dysregulation of calcium handling is implicated in heart disease.
Purpose of the Study:
- To investigate the mechanisms of impaired EC coupling in cardiac hypertrophy and heart failure.
- To examine the relationship between plasma membrane calcium current (ICa) and sarcoplasmic reticulum (SR) calcium release.
- To determine the role of beta-adrenergic stimulation in overcoming EC coupling defects.
Main Methods:
- Studied single myocytes from hypertensive (Dahl SS/Jr) and heart failure (SH-HF) rats.
- Utilized confocal microscopy and patch-clamp techniques.
- Visualized calcium sparks to assess SR calcium release evoked by ICa.
Main Results:
- The ability of ICa to trigger SR calcium release was reduced in both hypertrophied and failing hearts.
- ICa density and SR calcium release channels were normal, indicating a defect in the coupling mechanism.
- Beta-adrenergic stimulation partially restored EC coupling in hypertrophy but not in heart failure.
Conclusions:
- A defect in the EC coupling process, specifically the interplay between sarcolemmal and SR calcium channels, contributes to cardiac dysfunction.
- This EC coupling defect, initially developing during hypertrophy, may progress to heart failure as compensatory mechanisms falter.
Abstract:
Cardiac hypertrophy and heart failure caused by high blood pressure were studied in single myocytes taken from hypertensive rats (Dahl SS/Jr) and SH-HF rats in heart failure. Confocal microscopy and patch-clamp methods were used to examine excitation-contraction (EC) coupling, and the relation between the plasma membrane calcium current (ICa) and evoked calcium release from the sarcoplasmic reticulum (SR), which was visualized as "calcium sparks." The ability of ICa to trigger calcium release from the SR in both hypertrophied and failing hearts was reduced. Because ICa density and SR calcium-release channels were normal, the defect appears to reside in a change in the relation between SR calcium-release channels and sarcolemmal calcium channels. beta-Adrenergic stimulation largely overcame the defect in hypertrophic but not failing heart cells. Thus, the same defect in EC coupling that develops during hypertrophy may contribute to heart failure when compensatory mechanisms fail.