Rat cardiac troponin T mutation (F72L)-mediated impact on thin filament cooperativity is divergently modulated by α- and β-myosin heavy chain isoforms

American Journal of Physiology. Heart and Circulatory Physiology
Vikram ChandraMurali Chandra

Abstract

The primary causal link between disparate effects of human hypertrophic cardiomyopathy (HCM)-related mutations in troponin T (TnT) and α- and β-myosin heavy chain (MHC) isoforms on cardiac contractile phenotype remains poorly understood. Given the divergent impact of α- and β-MHC on the NH2-terminal extension (44-73 residues) of TnT, we tested if the effects of the HCM-linked mutation (TnTF70L) were differentially altered by α- and β-MHC. We hypothesized that the emergence of divergent thin filament cooperativity would lead to contrasting effects of TnTF70L on contractile function in the presence of α- and β-MHC. The rat TnT analog of the human F70L mutation (TnTF72L) or the wild-type rat TnT (TnTWT) was reconstituted into demembranated muscle fibers from normal (α-MHC) and propylthiouracil-treated (β-MHC) rat hearts to measure steady-state and dynamic contractile function. TnTF72L-mediated effects on tension, myofilament Ca(2+) sensitivity, myofilament cooperativity, rate constants of cross-bridge (XB) recruitment dynamics, and force redevelopment were divergently modulated by α- and β-MHC. TnTF72L increased the rate of XB distortion dynamics by 49% in α-MHC fibers but had no effect in β-MHC fibers; these observations suggest ...Continue Reading

References

May 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·B Brenner, E Eisenberg
May 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·B Brenner
May 18, 1999·Journal of Molecular and Cellular Cardiology·M ChandraR J Solaro
Apr 4, 2000·Physiological Reviews·A M GordonM Regnier
Apr 5, 2000·The Journal of Biological Chemistry·A C OliveiraJ L Silva
Jun 13, 2001·Annals of Biomedical Engineering·K B CampbellB K Slinker
Aug 22, 2001·American Journal of Physiology. Heart and Circulatory Physiology·T J HerronK S McDonald
May 16, 2002·The Journal of Biological Chemistry·Larry S TobacmanEarl Homsher
Mar 17, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Kenneth B CampbellWilliam C Hunter
Oct 9, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Veronica L M RundellPieter P de Tombe
Jul 5, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Murali ChandraJil C Tardiff
Jan 31, 2006·Biophysical Journal·Murali ChandraKenneth B Campbell
Dec 2, 2006·The Journal of Physiology·Julian E StelzerRichard L Moss
Jul 13, 2007·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Murali ChandraKenneth B Campbell
Aug 25, 2007·The Journal of Physiology·Pieter P de Tombe, G J M Stienen
Sep 9, 2009·The Journal of Physiology·Buel D RodgersLuis F Santana
Nov 17, 2009·Journal of Molecular and Cellular Cardiology·Ruth H WillottJames D Potter
Jul 28, 2010·The Journal of General Physiology·Steven J FordKenneth B Campbell
Jul 30, 2011·Circulation Journal : Official Journal of the Japanese Circulation Society·Toru KuboYoshinori L Doi
Aug 14, 2012·Journal of Molecular and Cellular Cardiology·Steven J FordMurali Chandra
Sep 27, 2012·Biophysical Journal·Sampath K GollapudiMurali Chandra
Sep 18, 2013·The Journal of General Physiology·Ranganath Mamidi, Murali Chandra
Nov 12, 2013·Biophysical Journal·Ranganath MamidiMurali Chandra
Feb 15, 2015·American Journal of Physiology. Heart and Circulatory Physiology·Sampath K GollapudiMurali Chandra

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Citations

Oct 23, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Alexis V MickelsonMurali Chandra
Feb 2, 2019·The Journal of General Physiology·Joel C RobinettKerry S McDonald
Jan 4, 2019·The Journal of General Physiology·Sherif M RedaMurali Chandra
May 20, 2018·The Journal of General Physiology·Sherif M Reda, Murali Chandra
Aug 27, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Alexis V Mickelson, Murali Chandra

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