Gene transfer replacement of native TnI with embryonic/fetal isoforms markedly enhanced the Ca(2+) sensitivity of tension development, whereas TnT or Tm isoform replacement did not.
Troponin I (TnI) embryonic/fetal isoform replacement enhances calcium sensitivity of tension development, identifying it as a potential target to modify contractile performance in myocardium.
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 Ca(2+) 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.
Metzger et al. (Tue,) conducted a other in Cardiac contraction. Gene transfer of embryonic/fetal isoforms of Tm, TnT, and TnI vs. Native isoforms was evaluated on Ca(2+) sensitivity of tension development. Gene transfer replacement of native TnI with embryonic/fetal isoforms markedly enhanced the Ca(2+) sensitivity of tension development, whereas TnT or Tm isoform replacement did not.
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