Differences in mechanisms of SR dysfunction in ischemic vs. idiopathic dilated cardiomyopathy

We examined 1) contractile properties and the intracellular Ca2+ concentration ([Ca2+](i)) transient in cardiac myocytes and 2) sarcoplasmic reticulum (SR) Ca2+ 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 [Ca2+](i) was decreased 27 +/- 9% and diastolic [Ca2+](i) was increased 36 +/- 11%. In ICM the diastolic [Ca2+](i) was increased 59 +/- 12% but the systolic [Ca2+](i) was unchanged. A significant decrease of the ATP-dependent SR Ca2+ uptake rate associated with the reduction of the SR Ca2+-ATPase protein level was found in ICM. In contrast, the significant decrease in SR Ca2+ release rate was distinct in DCM. The large amount of Ca2+ 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 Ca2+ release channel gating property in DCM. We conclude that potentially important differences exist in the intracellular Ca2+ homeostasis and excitation-contraction coupling in ICM vs. DCM. The SR Ca2+ release dysfunction may play an important pathogenetic role in the abnormal Ca2+ homeostasis in DCM, and the SR Ca2+ uptake dysfunction may be responsible for the contractile dysfunction in ICM.