Myosin heavy chain and cardiac troponin T damage is associated with impaired myofibrillar ATPase activity contributing to sarcomeric dysfunction in Ca2+-paradox rat hearts.

Abstract:

:This study aimed to explore the potential contribution of myofibrils to contractile dysfunction in Ca2+-paradox hearts. Isolated rat hearts were perfused with Krebs-Henseleit solution (Control), followed by Ca2+-depletion, and then Ca2+-repletion after Ca2+-depletion (Ca2+-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 Ca2+-depletion (9.8 ± 1.3 mmHg) and Ca2+-paradox (12.9 ± 1.3 mmHg) with similar decline in +dP/dt and -dP/dt. LVEDP was increased in both Ca2+-depletion and Ca2+-paradox. Compared to Control, myofibrillar Ca2+-stimulated ATPase activity was decreased in the Ca2+-depletion group (12.08 ± 0.57 vs. 8.13 ± 0.19 µmol Pi/mg protein/h), besides unvarying Mg2+ ATPase activity, while upon Ca2+-paradox myofibrillar Ca2+-stimulated ATPase activity was decreased (12.08 ± 0.57 vs. 8.40 ± 0.22 µmol Pi/mg protein/h), but Mg2+ ATPase activity was increased (3.20 ± 0.25 vs. 7.21 ± 0.36 µmol Pi/mg protein/h). In force measurements of isolated cardiomyocytes at saturating [Ca2+], Ca2+-depleted cells had lower rate constant of force redevelopment (k tr,max, 3.85 ± 0.21) and unchanged active tension, while those in Ca2+-paradox produced lower active tension (12.12 ± 3.19 kN/m2) and k tr,max (3.21 ± 23) than cells of Control group (25.07 ± 3.51 and 4.61 ± 22 kN/m2, respectively). In biochemical assays, α-myosin heavy chain and cardiac troponin T presented progressive degradation during Ca2+-depletion and Ca2+-paradox. Our results suggest that contractile impairment in Ca2+-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 Ca2+-paradoxical hearts is apparently not related to titin, rather explained by the altered myofibrillar ATPase activity.

journal_name

Mol Cell Biochem

authors

Kovács Á,Kalász J,Pásztor ET,Tóth A,Papp Z,Dhalla NS,Barta J

doi

10.1007/s11010-017-2954-8

subject

Has Abstract

pub_date

2017-06-01 00:00:00

pages

57-68

issue

1-2

eissn

0300-8177

issn

1573-4919

pii

10.1007/s11010-017-2954-8

journal_volume

430

pub_type

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