Altered diastolic [Ca2+]i handling in human ventricular myocytes from patients with terminal heart failure.
To investigate whether the slow diastolic decay of [Ca2+]i in myocardium of patients with heart failure is a result of alterations of the Ca2+ adenosine triphosphatase of the sarcoplasmic reticulum of the sarcolemma, [Ca2+]i transients were recorded in voltage-clamped ventricular cells isolated from hearts of patients with terminal heart failure or from undiseased donor hearts. To isolate the [Ca2+]i-reuptake function of the sarcoplasmic reticulum, myocytes were dialyzed via the patch pipette with Na(+)-free solution and incubated in Ca(2+)-free and Na(+)-free solution to inhibit Na+/Ca2+ exchange. After superfusion with Ca(2+)-containing, Na(+)-free medium, the sarcoplasmic reticulum was loaded with Ca2+ through repetitive voltage-clamp pulses to +10 mV. Under these conditions, [Ca2+]i decay was significantly slower in myocytes from patients with heart failure (538 +/- 66 msec) than in controls (305 +/- 16 msec; p < 0.05). After the addition of 10 mmol/L of caffeine, [Ca2+]i levels did not show appreciable decay between two voltage-clamp pulses in diseased and undiseased myocytes. We conclude that diastolic decay of [Ca2+]i in ventricular myocytes from patients with terminal heart failure is partially the result of a decreased rate of Ca2+ reuptake by the sarcoplasmic reticulum. Sarcolemmal Ca2+ adenosine triphosphatase does not contribute significantly to cytoplasmic [Ca2+]i removal during an individual heartbeat.
Beuckelmann
D J
DJ
Department of Medicine III, University of Cologne, Germany.
Näbauer
M
M
Krüger
C
C
Erdmann
E
E
D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000502:physiology; D002478:Cells, Cultured; D003971:Diastole / Q000502:physiology*; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D012508:Sarcolemma / Q000201:enzymology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D000252:Calcium-Transporting ATPases; D002118:Calcium