Titin isoform variance and length dependence of activation in skinned bovine cardiac muscle

Norio Fukuda, Yiming Wu, Gerrie Farman, Thomas C. Irving, Henk Granzier

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

We have explored the role of the giant elastic protein titin in the Frank-Starling mechanism of the heart by measuring the sarcomere length (SL) dependence of activation in skinned cardiac muscles with different titin-based passive stiffness characteristics. We studied muscle from the bovine left ventricle (BLV), which expresses a high level of a stiff titin isoform, and muscle from the bovine left atrium (BLA), which expresses more compliant titin isoforms. Passive tension was also varied in each muscle type by manipulating the pre-history of stretch prior to activation. We found that the SL-dependent increases in Ca2+ sensitivity and maximal Ca2+-activated tension were markedly more pronounced when titin-based passive tension was high. Small-angle X-ray diffraction experiments revealed that the SL dependence of reduction of interfilament lattice spacing is greater in BLV than in BLA and that the lattice spacing is coupled with titin-based passive tension. These results support the notion that titin-based passive tension promotes actomyosin interaction by reducing the lattice spacing. This work indicates that titin may be a factor involved in the Frank-Starling mechanism of the heart by promoting actomyosin interaction in response to stretch.

Original languageEnglish (US)
Pages (from-to)147-154
Number of pages8
JournalJournal of Physiology
Volume553
Issue number1
DOIs
StatePublished - Nov 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Physiology

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