Calcium Content of the Sarcoplasmic Reticulum in Isolated Ventricular Myocytes from Patients with Terminal Heart Failure

Abstract

Systolic [Ca²⁺]_i-transients have been shown to be depressed in isolated ventricular myocytes from patients with terminal heart failure compared to controls. Experiments were performed in human ventricular cells to investigate whether this reduced systolic [Ca²⁺]_i-transient may be due to a decreased Ca²⁺-content of the sarcoplasmic reticulum (SR). Single myocytes were isolated from left ventricular myocardium of patients with terminal heart failure undergoing cardiac transplantation. These results were compared to those obtained from cells of healthy donor hearts that were not suitable for transplantation for technical reasons. [Ca²⁺]_i-transients were recorded from isolated cells under voltage clamp perfused internally with the Ca²⁺-indicator fura-2. The Ca²⁺-content of the SR was estimated by rapid extracellular application of caffeine (10 mm) to open the Ca²⁺-release channel of the SR and comparison of the caffeine-induced [Ca²⁺]_i-transients in cells from patients with heart failure and from controls without heart failure. Upon steady-state depolarizations to +10 mV (maximum of the Ca²⁺-current), [Ca²⁺]_i-transients in cells from patients with heart failure were significantly smaller than in myocytes from undiseased hearts (333±26v596±80 nm,P<0.05). Application of caffeine caused a [Ca²⁺]_i-transient that was always larger than during depolarization. Caffeine-induced [Ca²⁺]_i-transients were significantly smaller in cells from diseased hearts compared with controls (970±129v2586±288 nm,P<0.01). A positive correlation was found between left ventricular ejection fraction and caffeine-induced [Ca²⁺]_i-transients in these cells. It is concluded, that depressed [Ca²⁺]_i-transients in myocytes from patients with heart failure may be caused by a decreased Ca²⁺-content of the SR possibly due to an altered Ca²⁺-ATPase activity in these hearts. It is not necessary to postulate an additional defect of the Ca²⁺-release function of the SR to account for the alterations of intracellular (Ca²⁺]_i-handling.