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Subcellular creatine kinase alterations. Implications in heart failure
E De Sousa1, V Veksler, A Minajeva
1Cardiologie Cellulaire et Moléculaire, U-446 INSERM, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France.
Circulation Research
|July 13, 1999
Summary
Decreased creatine kinase (CK) function in heart failure impairs energy supply and calcium handling. This study in rats reveals altered CK activity contributes to energy flux and calcium homeostasis changes in congestive heart failure.
Area of Science:
- Biochemistry
- Cardiology
- Physiology
Background:
- Congestive heart failure (CHF) involves complex metabolic and functional changes.
- Creatine kinase (CK) plays a crucial role in cellular energy buffering and transport.
Purpose of the Study:
- To investigate the role of creatine kinase (CK) functioning in energy metabolism and calcium homeostasis in a rat model of congestive heart failure (CHF).
Main Methods:
- Induction of heart failure via aortic banding in young rats.
- In situ analysis of myofilaments, sarcoplasmic reticulum (SR), and mitochondrial functions using selective membrane permeabilization.
- Assessment of CK activity, content (Western blots), and compartmentation in cardiac fibers.
Main Results:
- Significant reduction in mitochondrial CK activity and content, and M-isoform CK (MM-CK) activity in failing hearts.
- Decreased myofibrillar force and crossbridge kinetics, with unaltered calcium sensitivity.
- Impaired SR calcium uptake capacity and reduced efficiency of phosphocreatine in enhancing uptake.
- Diminished myocardial oxidative capacity and impaired respiratory control by adenine nucleotides.
Conclusions:
- Alterations in CK compartmentation, particularly mitochondrial CK, are evident in CHF.
- These CK changes contribute to impaired energy fluxes and disrupted calcium homeostasis in the failing heart.
- Findings highlight CK's role in cardiac energy dynamics and suggest therapeutic targets for heart failure.