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

G. M. Arteaga, K. A. Palmiter, J. M. Leiden, R. J. Solaro

Research output: Contribution to journalArticle

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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
StatePublished - 2000
Externally publishedYes

Fingerprint

Sarcomeres
Troponin I
Myofibrils
Transgenic Mice
Calcium
calmidazolium
EMD 53998
BA 41899
Myosins
Actins
Detergents
Heart Ventricles

ASJC Scopus subject areas

  • Physiology

Cite this

Attenuation of length dependence of calcium activation in myofilaments of transgenic mouse hearts expressing slow skeletal troponin I. / Arteaga, G. M.; Palmiter, K. A.; Leiden, J. M.; Solaro, R. J.

In: Journal of Physiology, Vol. 526, No. 3, 2000, p. 541-549.

Research output: Contribution to journalArticle

Arteaga, G. M. ; Palmiter, K. A. ; Leiden, J. M. ; Solaro, R. J. / Attenuation of length dependence of calcium activation in myofilaments of transgenic mouse hearts expressing slow skeletal troponin I. In: Journal of Physiology. 2000 ; Vol. 526, No. 3. pp. 541-549.
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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.",
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AB - 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.

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