Cooperative cross-bridge activation of thin filaments contributes to the Frank-Starling mechanism in cardiac muscle

L. Smith, C. Tainter, M. Regnier, D. A. Martyn

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Myosin cross-bridges play an important role in the regulation of thin-filament activation in cardiac muscle. To test the hypothesis that sarcomere length (SL) modulation of thin-filament activation by strong-binding cross-bridges underlies the Frank-Starling mechanism, we inhibited force and strong cross-bridge binding to intermediate levels with sodium vanadate (Vi). Force and stiffness varied proportionately with [Ca2+] and [Vi]. Increasing [Vi] (decreased force) reduced the pCa50 of force-[Ca 2+] relations at 2.3 and 2.0 μm SL, with little effect on slope (nH). When maximum force was inhibited to ∼40%, the effects of SL on force were diminished at lower [Ca2+], whereas at higher [Ca 2+] (pCa < 5.6) the relative influence of SL on force increased. In contrast, force inhibition to ∼20% significantly reduced the sensitivity of force-[Ca2+] relations to changes in both SL and myofilament lattice spacing. Strong cross-bridge binding cooperatively induced changes in cardiac troponin C structure, as measured by dichroism of 5′ iodoacetamido-tetramethylrhodamine-labeled cardiac troponin C. This apparent cooperativity was reduced at shorter SL. These data emphasize that SL and/or myofilament lattice spacing modulation of the cross-bridge component of cardiac thin-filament activation contributes to the Frank-Starling mechanism.

Original languageEnglish (US)
Pages (from-to)3692-3702
Number of pages11
JournalBiophysical Journal
Volume96
Issue number9
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics

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