Functional consequence of mutation in rat cardiac troponin T is affected differently by myosin heavy chain isoforms.

The Journal of Physiology
Matthew L TschirgiMurali Chandra

Abstract

Cardiac troponin T (cTnT) is an essential component of the thin filament regulatory unit (RU) that regulates Ca2+ activation of tension in the heart muscle. Because there is coupling between the RU and myosin crossbridges, the functional outcome of cardiomyopathy-related mutations in cTnT may be modified by the type of myosin heavy chain (MHC) isoform. Ca2+ activation of tension and ATPase activity were measured in muscle fibres from normal rat hearts containing alpha-MHC isoform and propylthiouracil (PTU)-treated rat hearts containing beta-MHC isoform. Muscle fibres from normal and PTU-treated rat hearts were reconstituted with two different mutations in rat cTnT; the deletion of Glu162 (cTnT(E162DEL)) and the deletion of Lys211 (cTnT(K211DEL)). Alpha-MHC and beta-MHC isoforms had contrasting impact on tension-dependent ATP consumption (tension cost) in cTnT(E162DEL) and cTnT(K211DEL) reconstituted muscle fibres. Significant increases in tension cost in alpha-MHC-containing muscle fibres corresponded to 17% (P < 0.01) and 23% (P < 0.001) when reconstituted with cTnT(E162DEL) and cTnT(K211DEL), respectively. In contrast, tension cost decreased when these two cTnT mutants were reconstituted in muscle fibres containing beta-MHC; ...Continue Reading

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Citations

Sep 18, 2013·The Journal of General Physiology·Ranganath Mamidi, Murali Chandra
Aug 14, 2012·Journal of Molecular and Cellular Cardiology·Steven J FordMurali Chandra
Oct 22, 2014·PloS One·Georges HajjeNassim Farès
Jul 6, 2011·The Journal of Physiology·Yuefang ZhouHenry J Kaminski
Feb 15, 2015·American Journal of Physiology. Heart and Circulatory Physiology·Sampath K GollapudiMurali Chandra
Jan 4, 2019·The Journal of General Physiology·Sherif M RedaMurali Chandra
Jul 13, 2007·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Murali ChandraKenneth B Campbell
Sep 6, 2015·American Journal of Physiology. Heart and Circulatory Physiology·Vikram ChandraMurali Chandra

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