Identification of a region of troponin I important in signaling cross-bridge-dependent activation of cardiac myofilaments

Patti L. Engel, Tomoyoshi Kobayashi, Brandon Biesiadecki, Jonathan Davis, Svetlana Tikunova, Steven Wu, R. John Solaro

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Force generating strong cross-bridges are required to fully activate cardiac thin filaments, but the molecular signaling mechanism remains unclear. Evidence demonstrating differential extents of cross-bridge-dependent activation of force, especially at acidic pH, in myofilaments in which slow skeletal troponin I (ssTnI) replaced cardiac TnI (cTnI) indicates the significance of a His in ssTnI that is an homologous Ala in cTnI. We compared cross-bridge- dependent activation in myofilaments regulated by cTnI, ssTnI, cTnI(A66H), or ssTnI(H34A). A drop from pH7.0 to 6.5 induced enhanced cross-bridge-dependent activation in cTnI myofilaments, but depressed activation in cTnI(A66H) myofilaments. This same drop in pH depressed crossbridge-dependent activation in both ssTnI myofilaments and ssTnI(H34A) myofilaments. Compared with controls, cTnI(A66H) myofilaments were desensitized to Ca2+, whereas there was no difference in the Ca2+-force relationship between ssTnI and ssTnI(H34A) myofilaments. The mutations in cTnI and ssTnI did not affect Ca 2+ dissociation rates from cTnC at pH7.0 or 6.5. However, at pH6.5, cTnI(A66H) had lower affinity for cTnT than cTnI. We also probed cross-bridge-dependent activation in myofilaments regulated by cTnI(Q56A). Myofilaments containing cTnI(Q56A) demonstrated cross-bridge-dependent activation that was similar to controls containing cTnI at pH 7.0 and an enhanced cross-bridge-dependent activation at pH 6.5. We conclude that a localized N-terminal region of TnI comprised ofamino acids 33-80, which interacts with C-terminal regions of cTnC and cTnT, is of particular significance in transducing signaling of thin filament activation by strong cross-bridges.

Original languageEnglish (US)
Pages (from-to)183-193
Number of pages11
JournalJournal of Biological Chemistry
Volume282
Issue number1
DOIs
StatePublished - Jan 5 2007

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