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Ca2+ uptake by cardiac sarcoplasmic reticulum from patients with idiopathic dilated cardiomyopathy
M A Movsesian1, M R Bristow, J Krall
1Cardiology Division, University of Utah Medical Center, Salt Lake City 84108.
Insights
Calcium handling in human hearts with dilated cardiomyopathy is not due to sarcoplasmic reticulum issues. This study found normal calcium uptake in failing hearts, suggesting other mechanisms are at play.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Biochemistry
Background:
- Idiopathic dilated cardiomyopathy (IDCM) is a significant cause of heart failure in humans.
- Abnormal calcium (Ca2+) handling is implicated in the pathophysiology of heart failure.
- Sarcoplasmic reticulum (SR) plays a crucial role in regulating intracellular Ca2+ concentrations.
Purpose of the Study:
- To investigate the intrinsic Ca2+ uptake function of the sarcoplasmic reticulum in human hearts with IDCM.
- To compare Ca2+ uptake kinetics and beta-receptor density in failing versus nonfailing human ventricular myocardium.
Main Methods:
- Preparation of sarcoplasmic reticulum from left ventricular myocardium of nonfailing and IDCM (Class IV) human hearts.
- Measurement of Ca2+ uptake kinetics (Vmax, K0.5, nHill) by sarcoplasmic reticulum.
- Quantification of beta-receptor density in crude sarcolemma.
Main Results:
- Ca2+ uptake by sarcoplasmic reticulum showed no significant difference between nonfailing (Vmax: 593 +/- 82 nmol/mg-min) and failing hearts (Vmax: 593 +/- 36 nmol/mg-min).
- Kinetic parameters (K0.5 and nHill) for Ca2+ uptake were similar in both groups.
- Beta-receptor density was significantly lower in failing hearts (52.1 +/- 4.5 fmol/mg) compared to nonfailing donors (110.0 +/- 15.3 fmol/mg).
Conclusions:
- Intrinsic Ca2+ uptake by sarcoplasmic reticulum is not impaired in human idiopathic dilated cardiomyopathy.
- Abnormal Ca2+ handling in IDCM likely results from mechanisms other than intrinsic sarcoplasmic reticulum Ca2+ uptake dysfunction.
- Reduced beta-receptor density in failing hearts may contribute to altered cardiac function.
Abstract:
We measured Ca2+ uptake by sarcoplasmic reticulum prepared from left ventricular myocardium obtained from six nonfailing human hearts and nine excised hearts from patients with class IV idiopathic dilated cardiomyopathy. Ca2+ uptake had a Vmax of 593 +/- 82 nmol/mg-min, a K0.5 of 0.68 +/- 0.07 microM, and an nHill of 1.7 +/- 0.1 in the nonfailing hearts. The corresponding values in the excised failing hearts were 593 +/- 36 nmol/mg-min, 0.63 +/- 0.03 microM, and 1.6 +/- 0.1. The beta-receptor density in crude sarcolemma prepared from left ventricular myocardium was 110.0 +/- 15.3 fmol/mg in the unmatched donors and 52.1 +/- 4.5 fmol/mg in the excised failing hearts. These results suggest that abnormal Ca2+ handling in idiopathic dilated cardiomyopathy in humans is not the result of any intrinsic alteration of Ca2+ uptake by sarcoplasmic reticulum.