1998
DOI: 10.1152/ajpcell.1998.275.1.c200
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Ca2+-sensitizing effects of the mutations at Ile-79 and Arg-92 of troponin T in hypertrophic cardiomyopathy

Abstract: Several mutations in human cardiac troponin T (TnT) gene have been reported to cause hypertrophic cardiomyopathy (HCM). To explore the effects of the mutations on cardiac muscle contractile function under physiological conditions, human cardiac TnT mutants, Ile79Asn and Arg92Gln, as well as wild type, were expressed in Escherichia coli and exchanged into permeabilized rabbit cardiac muscle fibers, and Ca2+-activated force was determined. The free Ca2+ concentrations required for tension generation were found t… Show more

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Cited by 113 publications
(83 citation statements)
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“…skinned cardiac muscle fibers before and after exchanging native cTnT with recombinant human wild-type or ⌬K210 cTnT. Treatment of skinned fibers with an excess amount of recombinant human cTnT resulted in a decrease in the amount of endogenous cTnI and cTnC (lanes 3 and 4) because of displacement of the Tn complex with recombinant human cTnT, as demonstrated in our previous studies (10,14,(30)(31)(32). Subsequent incubation with rabbit cTnI and cTnC accomplished the exchange of recombinant human cTnT into rabbit cardiac muscle fibers (lanes 5 and 6).…”
Section: Preparation Of Skinned Fibers and Force Measurementssupporting
confidence: 72%
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“…skinned cardiac muscle fibers before and after exchanging native cTnT with recombinant human wild-type or ⌬K210 cTnT. Treatment of skinned fibers with an excess amount of recombinant human cTnT resulted in a decrease in the amount of endogenous cTnI and cTnC (lanes 3 and 4) because of displacement of the Tn complex with recombinant human cTnT, as demonstrated in our previous studies (10,14,(30)(31)(32). Subsequent incubation with rabbit cTnI and cTnC accomplished the exchange of recombinant human cTnT into rabbit cardiac muscle fibers (lanes 5 and 6).…”
Section: Preparation Of Skinned Fibers and Force Measurementssupporting
confidence: 72%
“…The decrease in Ca 2ϩ sensitivity of force generation also is expected to facilitate the relaxation of the cardiac muscle at diastole and might directly explain the cardiac dilation itself to some extent. In contrast, we have previously shown that the mutations in cTnT associated with HCM have Ca 2ϩ -sensitizing effects on force generation in cardiac muscle (10)(11)(12)(13)(14)(15). The increase in Ca 2ϩ sensitivity of force generation is expected to impair the relaxation of cardiac muscle and thus cause a diastolic dysfunction, which might be directly involved in the high incidence of sudden death despite mild or no hypertrophy in HCM patients associated with cTnT mutations.…”
Section: Discussionmentioning
confidence: 88%
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