Sarcomere thin filament regulatory isoforms: Evidence of a dominant effect of slow skeletal troponin I on cardiac contraction

Joseph M. Metzger, Daniel E. Michele, Elizabeth M. Rust, Andrea R. Borton, Margaret V. Westfall

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Thin filament proteins tropomyosin (Tm), troponin T (TnT), and troponin I (TnI) form an allosteric regulatory complex that is required for normal cardiac contraction. Multiple isoforms of TnT, Tm, and TnI are differentially expressed in both cardiac development and disease, but concurrent TnI, Tm, and TnT isoform switching has hindered assignment of cellular function to these transitions. We systematically incorporated into the adult sarcomere the embryonic/fetal isoforms of Tm, TnT, and TnI by using gene transfer. In separate experiments, greater than 90% of native TnI and 40-50% of native Tm or TnT were specifically replaced. The Ca2+ sensitivity of tension development was markedly enhanced by TnI replacement but not by TnT or Tm isoform replacement. Titration of TnI replacement from >90% to <30% revealed a dominant functional effect of slow skeletal TnI to modulate regulation. Over this range of isoform replacement, TnI, but not Tm or TnT embryonic isoforms, influenced calcium regulation of contraction, and this identifies TnI as a potential target to modify contractile performance in normal and diseased myocardium.

Original languageEnglish (US)
Pages (from-to)13118-13123
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number15
DOIs
StatePublished - Apr 11 2003

Fingerprint Dive into the research topics of 'Sarcomere thin filament regulatory isoforms: Evidence of a dominant effect of slow skeletal troponin I on cardiac contraction'. Together they form a unique fingerprint.

  • Cite this