Attenuation of length dependence of calcium activation in myofilaments of transgenic mouse hearts expressing slow skeletal troponin I

Grace M. Arteaga, Kimberly A. Palmiter, Jeffrey M. Leiden, R. John Solaro

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Abstract

1. We compared sarcomere length (SL) dependence of the Ca2+-force relation of detergent-extracted bundles of fibres dissected from the left ventricle of wild-type (WT) and transgenic mouse hearts expressing slow skeletal troponin I (ssTnI-TG). Fibre bundles from the hearts of the ssTnI-TG demonstrated a complete replacement of the cardiac troponin I (cTnI) by ssTnI. 2. Compared to WT controls, ssTnI-TG fibre bundles were more sensitive to Ca2+ at both short SL (1· ± 0·1 μm) and long SL 2·3 ± 0·1 μm). However, compared to WT controls, the increase in Ca2+ sensitivity (change in half-maximally activating free Ca2+; ΔEC50) associated with the increase in SL was significantly blunted in the ssTnI-TG myofilaments. 3. Agents that sensitize the myofilaments to Ca2+ by promoting the actin-myosin reaction (EMD 57033 and CGP-48506) significantly reduced the length-dependent ΔEC50 for Ca2+ activation, when SL in WT myofilaments was increased from 1·9 to 2·3 μm. 4. Exposure of myofilaments to calmidazolium (CDZ), which binds to cTnC and increases its affinity for Ca2+, sensitized force developed by WT myofilaments to Ca2+ at SL 1·9 μm and desensitized the WT myofilaments at SL 2·3 μm. There were no significant effects of CDZ on ssTnI-TG myofilaments at either SL. 5. Our results indicate that length-dependent Ca2+ activation is modified by specific changes in thin filament proteins and by agents that promote the actin-myosin interaction. Thus, these in vitro results provide a basis for using these models to test the relative significance of the length dependence of activation in situ.

Original languageEnglish (US)
Pages (from-to)541-549
Number of pages9
JournalJournal of Physiology
Volume526
Issue number3
DOIs
StatePublished - Jan 1 2000

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ASJC Scopus subject areas

  • Physiology

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