Title
Phosphorylation-dependent alteration in myofilament <tex>$Ca^{2+}$</tex> sensitivity but normal mitochondrial function in septic heart Phosphorylation-dependent alteration in myofilament <tex>$Ca^{2+}$</tex> sensitivity but normal mitochondrial function in septic heart
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
New York ,
Subject
Human medicine
Source (journal)
American journal of respiratory and critical care medicine. - New York, 1994, currens
Volume/pages
163(2001) :2 , p. 362-367
ISSN
1073-449X
ISI
000167050900015
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
The subcellular mechanisms responsible for myocardial depression during sepsis remain unclear. Recent data suggest a role for impaired energy generation and utilization, resulting in altered contractile function. Here, we studied the energetic and mechanical properties of skinned fibers isolated from rabbit ventricle in a nonlethal but hypotensive model of endotoxemia. Thirty-six hours after (lipopolysaccharide (LPS) injection tin the presence of altered myocardial contractility), mitochondrial respiration, coupling between oxidation and phosphorylation, and creatine kinase function were similar in preparations from endotoxemic: (LPS) and control animals. The maximal Ca2+-activated force was similar in LPS and control preparations. However, the Ca2+ concentration corresponding to half-maximal force (pCa(50) where pCa = -log(10)[Ca2+]) was 5.55 +/- 0.01 (n = 11) in LPS fibers versus 5.61 +/- 0.01 (n = 10) in control fibers (p < 0.01). Both protein kinase A (PKA) and alkaline phosphatase treatment led to the disappearance in the difference between control and LPS pCa(50) values. Incubation of control fibers with the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) did not change the Ca2+ sensitivity after subsequent skinning, whereas isoproterenol decreased pCa(50) from 5.62 +/- 0.01 to 5.55 +/- 0.01 (p < 0.01). These data suggest that during sepsis, cardiac mitochondrial and creatine kinase systems remain unaltered, whereas protein phosphorylation decreases myofibrillar Ca2+ sensitivity and may contribute to the depression of cardiac contractility.
E-info
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