Differences in mechanisms of SR dysfunction in ischemic vs. idiopathic dilated cardiomyopathy.
We examined 1) contractile properties and the intracellular Ca(2+) concentration ([Ca(2+)](i)) transient in cardiac myocytes and 2) sarcoplasmic reticulum (SR) Ca(2+) uptake and release function in myocardium from patients with end-stage heart failure caused by ischemic (ICM) vs. idiopathic dilated cardiomyopathy (DCM). The amplitude of cell motion was decreased 43 +/- 6% in ICM and 68 +/- 7% in DCM compared with that in normal organ donors (DN). Time to peak of shortening was increased 43 +/- 15% in DCM, but not in ICM. Prolongation of the relaxation time was more predominant in ICM. In DCM the systolic [Ca(2+)](i) was decreased 27 +/- 9% and diastolic [Ca(2+)](i) was increased 36 +/- 11%. In ICM the diastolic [Ca(2+)](i) was increased 59 +/- 12% but the systolic [Ca(2+)](i) was unchanged. A significant decrease of the ATP-dependent SR Ca(2+) uptake rate associated with the reduction of the SR Ca(2+)-ATPase protein level was found in ICM. In contrast, the significant decrease in SR Ca(2+) release rate was distinct in DCM. The large amount of Ca(2+) retained in the SR associated with a significant decrease in the maximum reaction velocity and increase in the Michaelis-Menten constant in the caffeine concentration-response curve suggests a fundamental abnormality in the SR Ca(2+) release channel gating property in DCM. We conclude that potentially important differences exist in the intracellular Ca(2+) homeostasis and excitation-contraction coupling in ICM vs. DCM. The SR Ca(2+) release dysfunction may play an important pathogenetic role in the abnormal Ca(2+) homeostasis in DCM, and the SR Ca(2+) uptake dysfunction may be responsible for the contractile dysfunction in ICM.
Sen
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L
Division of Cardiology, Department of Medicine, Department of Surgery, University of California Los Angeles Medical Center, University of California Los Angeles School of Medicine, Los Angeles, California 90095, USA. lsen@mednet.ucla.edu
Cui
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Fonarow
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GC
Laks
H
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D000328:Adult; D000368:Aged; D002118:Calcium / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D012016:Reference Values; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D016277:Ventricular Function, Left
D002118:Calcium