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.
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
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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