Effects of troponin T mutations in familial hypertrophic cardiomyopathy on regulatory functions of other troponin subunits

F. Takahashi-Yanaga, I. Ohtsuki, S. Morimoto

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

We have previously shown that mutations in troponin T (TnT), which is associated with familial hypertrophic cardiomyopathy (HCM), cause an increase in the Ca2+ sensitivity and a potentiation of cardiac muscle contraction. To gain further insight into the pathophysiological role of these mutations, four mutations (Arg92Gln, Phe110Ile, Glu244Asp, Arg278Cys) were introduced into recombinant human cardiac TnT, and the mutants were exchanged into isolated porcine cardiac myofibrils. The effects of mutations were tested on maximal ATPase activity, the inhibitory function of troponin I (TnI) in the absence of troponin C (TnC), and the neutralizing function of TnC. Arg92Gln, Phe110Ile, and Glu244Asp markedly impaired the inhibitory function of TnI. Arg278Cys also impaired the inhibitory function of TnI, but the effect was much smaller. Phe110Ile and Glu244Asp markedly enhanced the neutralizing function of TnC and potentiated the maximum ATPase activity. Arg92Gln and Arg278Cys only slightly enhanced the neutralizing function of TnC, and they conferred no potentiation on the maximum ATPase activity. These results indicate that mutations in TnT impair multiple processes of Ca2+ regulation by troponin, and there are marked differences in the degree of impairment from mutation to mutation.

Original languageEnglish
Pages (from-to)127-131
Number of pages5
JournalJournal of biochemistry
Volume130
Issue number1
DOIs
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

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