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Myosin heavy chain and cardiac troponin T damage is associated with impaired myofibrillar ATPase activity contributing to sarcomeric dysfunction in Ca 2+ -paradox rat hearts
This study aimed to explore the potential contribution of myofibrils to contractile dysfunction in Ca -paradox hearts. Isolated rat hearts were perfused with Krebs-Henseleit solution (Control), followed by Ca -depletion, and then Ca -repletion after Ca -depletion (Ca -paradox) by Langendorff method....
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Published in: | Molecular and cellular biochemistry 2017-06, Vol.430 (1-2), p.57 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | This study aimed to explore the potential contribution of myofibrils to contractile dysfunction in Ca
-paradox hearts. Isolated rat hearts were perfused with Krebs-Henseleit solution (Control), followed by Ca
-depletion, and then Ca
-repletion after Ca
-depletion (Ca
-paradox) by Langendorff method. During heart perfusion left ventricular developed pressure (LVDP), end-diastolic pressure (LVEDP), rate of pressure development (+ dP/dt), and pressure decay (-dP/dt) were registered. Control LVDP (127.4 ± 6.1 mmHg) was reduced during Ca
-depletion (9.8 ± 1.3 mmHg) and Ca
-paradox (12.9 ± 1.3 mmHg) with similar decline in +dP/dt and -dP/dt. LVEDP was increased in both Ca
-depletion and Ca
-paradox. Compared to Control, myofibrillar Ca
-stimulated ATPase activity was decreased in the Ca
-depletion group (12.08 ± 0.57 vs. 8.13 ± 0.19 µmol P
/mg protein/h), besides unvarying Mg
ATPase activity, while upon Ca
-paradox myofibrillar Ca
-stimulated ATPase activity was decreased (12.08 ± 0.57 vs. 8.40 ± 0.22 µmol P
/mg protein/h), but Mg
ATPase activity was increased (3.20 ± 0.25 vs. 7.21 ± 0.36 µmol P
/mg protein/h). In force measurements of isolated cardiomyocytes at saturating [Ca
], Ca
-depleted cells had lower rate constant of force redevelopment (k
, 3.85 ± 0.21) and unchanged active tension, while those in Ca
-paradox produced lower active tension (12.12 ± 3.19 kN/m
) and k
(3.21 ± 23) than cells of Control group (25.07 ± 3.51 and 4.61 ± 22 kN/m
, respectively). In biochemical assays, α-myosin heavy chain and cardiac troponin T presented progressive degradation during Ca
-depletion and Ca
-paradox. Our results suggest that contractile impairment in Ca
-paradox partially resides in deranged sarcomeric function and compromised myofibrillar ATPase activity as a result of myofilament protein degradation, such as α-myosin heavy chain and cardiac troponin T. Impaired relaxation seen in Ca
-paradoxical hearts is apparently not related to titin, rather explained by the altered myofibrillar ATPase activity. |
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ISSN: | 1573-4919 |