{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T23:43:05Z","timestamp":1790120585873,"version":"4.0.1"},"reference-count":52,"publisher":"American Physiological Society","issue":"8","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["R01-HL-075643"],"award-info":[{"award-number":["R01-HL-075643"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>The primary causal link between disparate effects of human hypertrophic cardiomyopathy (HCM)-related mutations in troponin T (TnT) and \u03b1- and \u03b2-myosin heavy chain (MHC) isoforms on cardiac contractile phenotype remains poorly understood. Given the divergent impact of \u03b1- and \u03b2-MHC on the NH<jats:sub>2<\/jats:sub>-terminal extension (44\u201373 residues) of TnT, we tested if the effects of the HCM-linked mutation (TnT<jats:sub>F70L<\/jats:sub>) were differentially altered by \u03b1- and \u03b2-MHC. We hypothesized that the emergence of divergent thin filament cooperativity would lead to contrasting effects of TnT<jats:sub>F70L<\/jats:sub>on contractile function in the presence of \u03b1- and \u03b2-MHC. The rat TnT analog of the human F70L mutation (TnT<jats:sub>F72L<\/jats:sub>) or the wild-type rat TnT (TnT<jats:sub>WT<\/jats:sub>) was reconstituted into demembranated muscle fibers from normal (\u03b1-MHC) and propylthiouracil-treated (\u03b2-MHC) rat hearts to measure steady-state and dynamic contractile function. TnT<jats:sub>F72L<\/jats:sub>-mediated effects on tension, myofilament Ca<jats:sup>2+<\/jats:sup>sensitivity, myofilament cooperativity, rate constants of cross-bridge (XB) recruitment dynamics, and force redevelopment were divergently modulated by \u03b1- and \u03b2-MHC. TnT<jats:sub>F72L<\/jats:sub>increased the rate of XB distortion dynamics by 49% in \u03b1-MHC fibers but had no effect in \u03b2-MHC fibers; these observations suggest that TnT<jats:sub>F72L<\/jats:sub>augmented XB detachment kinetics in \u03b1-MHC, but not \u03b2-MHC, fibers. TnT<jats:sub>F72L<\/jats:sub>increased the negative impact of strained XBs on the force-bearing XBs by 39% in \u03b1-MHC fibers but had no effect in \u03b2-MHC fibers. Therefore, TnT<jats:sub>F72L<\/jats:sub>leads to contractile changes that are linked to dilated cardiomyopathy in the presence of \u03b1-MHC. On the other hand, TnT<jats:sub>F72L<\/jats:sub>leads to contractile changes that are linked to HCM in the presence of \u03b2-MHC.<\/jats:p>","DOI":"10.1152\/ajpheart.00519.2015","type":"journal-article","created":{"date-parts":[[2015,9,5]],"date-time":"2015-09-05T02:49:36Z","timestamp":1441421376000},"page":"H1260-H1270","source":"Crossref","is-referenced-by-count":15,"title":["Rat cardiac troponin T mutation (F72L)-mediated impact on thin filament cooperativity is divergently modulated by \u03b1- and \u03b2-myosin heavy chain isoforms"],"prefix":"10.1152","volume":"309","author":[{"given":"Vikram","family":"Chandra","sequence":"first","affiliation":[{"name":"Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sampath K.","family":"Gollapudi","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology and Neuroscience, Washington State 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