Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing human myocardium.
Expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase was shown to be reduced in failing human myocardium. The functional relevance of this finding, however, is not known. We investigated the relation between myocardial function and protein levels of SR Ca(2+)-ATPase in nonfailing human myocardium (8 muscle strips from 4 hearts) and in myocardium from end-stage failing hearts with dilated (10 muscle strips from 9 hearts) or ischemic (7 muscle strips from 5 hearts) cardiomyopathy. Myocardial function was evaluated by the force-frequency relation in isometrically contracting muscle strip preparations (37 degrees C, 30 to 180 min-1). In nonfailing myocardium, twitch tension rose with increasing rates of stimulation and was 76% higher at 120 min-1 compared with 30 min-1 (P < .02). In failing myocardium, there was no significant increase in average tension at stimulation rates above 30 min-1. At 120 min-1, twitch tension was decreased by 59% (P < .05) in dilated cardiomyopathy and 76% (P < .05) in ischemic cardiomyopathy compared with nonfailing myocardium. Protein levels of SR Ca(2+)-ATPase, normalized per total protein or per myosin, were reduced by 36% (P < .02) or 32% (P < .05), respectively, in failing compared with nonfailing myocardium. SR Ca(2+)-ATPase protein levels were closely related to SR Ca2+ uptake, measured in homogenates from the same hearts (r = .70, n = 16, and P < .005).(ABSTRACT TRUNCATED AT 250 WORDS)
Hasenfuss
G
G
Medizinische Klinik III, Universität Freiburg, Germany.
Reinecke
H
H
Studer
R
R
Meyer
M
M
Pieske
B
B
Holtz
J
J
Holubarsch
C
C
Posival
H
H
Just
H
H
Drexler
H
H
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000302:isolation & purification / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000201:enzymology / Q000503:physiopathology*; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000201:enzymology / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology*; D009218:Myosins / Q000032:analysis; D012016:Reference Values; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*
D009218:Myosins; D000252:Calcium-Transporting ATPases; D002118:Calcium