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Effect of calmodulin on sarcoplasmic reticular Ca2+-transport in the aging heart
C E Heyliger1, A R Prakash, J H McNeill
1Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Insights
Cardiac sarcoplasmic reticulum (SR) Ca2+ pump activity declines with age, even with calmodulin stimulation. This age-related reduction in SR Ca2+ transport may contribute to heart failure in older individuals.
Area of Science:
- Cardiovascular Physiology
- Aging Research
- Molecular Cardiology
Background:
- Heart failure is prevalent in the elderly, often linked to impaired myocardial contractility.
- Altered myocardial calcium (Ca2+) transport is implicated in age-related contractile dysfunction.
- The role of calmodulin, an endogenous activator, on sarcoplasmic reticulum (SR) Ca2+ pump activity in aging hearts is largely unknown.
Purpose of the Study:
- To investigate the Ca2+ pump activity of cardiac SR in aging myocardium.
- To assess the influence of calmodulin on SR Ca2+ transport in aged hearts.
- To provide insights into the molecular mechanisms of age-related cardiac dysfunction.
Main Methods:
- Utilized male Sprague-Dawley rats divided into young, middle-aged, and old age groups.
- Isolated purified sarcoplasmic reticulum (SR) membranes from ventricular tissues.
- Measured ATP-dependent Ca2+ accumulation by SR vesicles in the presence and absence of calmodulin.
Main Results:
- ATP-dependent Ca2+ accumulation was significantly depressed in middle-aged and old hearts compared to young hearts.
- This depression in Ca2+ transport was observed across all tested Ca2+ concentrations.
- Calmodulin stimulation did not restore SR Ca2+ pump activity to levels seen in younger hearts; activity was similar in middle-aged and old hearts.
Conclusions:
- The Ca2+ pump activity of cardiac SR is depressed in aging hearts.
- This age-related decline in SR Ca2+ transport persists even with calmodulin activation.
- Reduced SR Ca2+ pump function may be a contributing factor to the depressed contractile performance in elderly hearts.
Abstract:
Heart failure is common among the elderly and an alteration in myocardial Ca2+ transport is believed to be involved in its depressed contractile performance. Although ATP-dependent sarcoplasmic reticular (SR) Ca2+ transport has been reported to decrease in old hearts, virtually nothing appears to be known about the Ca2+ pump activity of SR in aging myocardium in the presence of calmodulin, one of its endogenous activators. In this study, the activity of the Ca2+ pump of aging cardiac SR was assessed in the presence of this endogenous stimulator. This assessment was therefore designed to give additional information about the status of this enzyme in old hearts. Male Sprague-Dawley rats were used and were divided into 3 groups: young (4-6 months old); middle-aged (15-17 months old) and old age (24-25 months old). Purified SR membranes were isolated from ventricular tissues. ATP-dependent Ca2+ accumulation by membrane vesicles of middle-aged and old hearts was significantly depressed in comparison to young hearts at all Ca2+ concentrations employed in the absence and presence of calmodulin. The activity of this Ca2+ transporter was similar in middle-aged and old hearts even in the presence of calmodulin. These results suggest that the activity of the Ca2+ pump in SR of aging hearts is depressed even in the presence of calmodulin.