Diminished posttetanic potentiation in failing human myocardium.
In heart failure a decreased function of SERCA 2 has been demonstrated. The present study aimed at investigating the relation between sarcoplasmic reticulum-Ca2+-load (SR-Ca2+-load) and the activity of the SERCA 2. SR-Ca2+ load was evaluated by measuring posttetanic potentiation (PTP) in human nonfailing (NF, n = 10) and endstage failing myocardium (DCM, n = 11). In addition, the effect of cyclopiazonic acid (CPA), a specific inhibitor of SERCA 2, on PTP was studied in both NF and DCM. In crude membrane preparations from the same hearts the maximal SERCA 2 activity was determined and correlated with the PTP. In failing myocardium the PTP was significantly reduced compared to nonfailing myocardium (13.7+/-0.75 mN/mm2 vs. 17.1+/-1.55 mN/mm2, p<0.05, +/- SEM). When PTP was studied in the presence of increased extracellular Ca2+-concentrations, the difference between NF and DCM was further pronounced. CPA decreased PTP in both nonfailing and failing human tissue. The maximal SERCA 2 activity was significantly reduced in failing myocardium (NF 267+/-18.5 nmol ATP/mg protein x min(-1) vs. DCM 191+/-13.4 nmol ATP/mg protein x min(-1), p<0.05, +/- SEM). Correlation of the PTP and maximal SERCA 2 activity revealed a close correlation between both parameters in NF and DCM. In summary, the presented results suggest that reduced SERCA 2 activity in DCM influences posttetanic force potentiation probably through a reduced SR-Ca2+-load.
Zobel
C
C
Universität zu Köln, Klinik III für Innere Medizin, Labor für Herzmuskelphysiologie und Molekulare Kardiologie, Köln, Germany.
Brixius
K
K
Bölck
B
B
Frank
K
K
Schwinger
R H
RH
D000328:Adult; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002303:Cardiac Output, Low / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology; D012016:Reference Values; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D004791:Enzyme Inhibitors; D007211:Indoles; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; C000543:cyclopiazonic acid