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This Article Full Text Full Text (PDF) All Versions of this Article: 574/1/263    most recent jphysiol.2006.107417v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tschirgi, M. L. Articles by Chandra, M. Search for Related Content PubMed PubMed Citation Articles by Tschirgi, M. L. Articles by Chandra, M. Related Collections Cardiovascular

¹ Department of Veterinary Comparative Anatomy Pharmacology and Physiology (VCAPP), 205 Wegner Hall, Washington State University, Pullman, WA 99164, USA

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 -MHC isoform and propylthiouracil (PTU)-treated rat hearts containing ß-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). -MHC and ß-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 -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 ß-MHC; by approximately 24% (P < 0.05) when reconstituted with cTnT_E162DEL and by approximately 17% (P = 0.09) when reconstituted with cTnT_K211DEL. Such differences in tension cost were substantiated by the mechano-dynamic analysis of cTnT mutant reconstituted muscle fibres from normal and PTU-treated rat hearts. Our observation demonstrates that qualitative changes in MHC isoform alters the nature of cardiac myofilament dysfunction induced by mutations in cTnT.

(Received 23 March 2006; accepted after revision 24 April 2006; first published online 27 April 2006)
Corresponding author M. Chandra: 205 Wegner Hall, Department of Veterinary Comparative Anatomy Pharmacology and Physiology (VCAPP), Washington State University, WA 99164, USA. Email: murali{at}vetmed.wsu.edu

This article has been cited by other articles:

				M. Chandra, M. L. Tschirgi, S. J. Ford, B. K. Slinker, and K. B. Campbell Interaction between myosin heavy chain and troponin isoforms modulate cardiac myofiber contractile dynamics Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1595 - R1607. [Abstract] [Full Text] [PDF]