Myocardial calcium cycling defect in furazolidone cardiomyopathy.
We have previously demonstrated that in furazolidone-induced congestive heart failure in turkeys the specific Ca(2+)-ATPase activity of myocardial sarcoplasmic reticulum (SR) is 60% increased in compensation for a 50% depression in net Ca(2+)-sequestration activity. This study tested the hypothesis that SR Ca(2+)-uptake and Ca(2+)-ATPase activities were uncoupled in this cardiomyopathy because of increased Ca(2+)-release channel activity. A novel microassay was used to monitor Ca2+ transport by myocardial homogenates using the fluorescent Ca2+ dye indo 1 to indicate extravesicular ionized Ca2+. The method is applied to cyropreserved biopsy specimens of myocardium and requires only 50 mg tissue. Both SR Ca(2+)-pump and SR Ca(2+)-channel activity were estimated using the channel-inhibitor ruthenium red (RR) and the mitochondrial inhibitor sodium azide. The specificity of the RR inhibition was confirmed using ryanodine. Cardiomyopathy was induced in 2-week-old turkey poults by the addition of 0.07% furazolidone to their feed for 4 weeks. Compared with controls, myocardial maximal Ca(2+)-channel activity relative to maximal Ca(2+)-pump activity was 22% greater and duration of Ca(2+)-channel activity was 100% increased. However, the heart failure birds had 43 and 53% decreases in absolute maximal Ca(2+)-pumping and Ca(2+)-channel activities, respectively. The abnormal Ca(2+)-channel activity resulted in 200% greater time before initiation of net Ca2+ sequestration and 700% greater final myocardial Ca2+ concentrations. For all birds, the Ca(2+)-accumulating activity was highly correlated with Ca(2+)-release activity (all p less than 0.05). These data indicate that in this animal model of congestive heart failure there is defective SR Ca(2+)-channel function resulting in abnormal Ca2+ homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)
O'Brien
P J
PJ
Department of Pathology, Ontario Veterinary College, University of Guelph, Canada.
Shen
H
H
Weiler
J E
JE
Mirsalimi
S M
SM
Julian
R J
RJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000502:physiology; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism*; D004195:Disease Models, Animal; D005664:Furazolidone; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014422:Turkeys
D015220:Calcium Channels; D005664:Furazolidone; D000252:Calcium-Transporting ATPases; D002118:Calcium