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 language | English (US) |
|---|---|
| Pages (from-to) | 541-549 |
| Number of pages | 9 |
| Journal | Journal of Physiology |
| Volume | 526 |
| Issue number | 3 |
| State | Published - 2000 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Attenuation of length dependence of calcium activation in myofilaments of transgenic mouse hearts expressing slow skeletal troponin I
AU - Arteaga, G. M.
AU - Palmiter, K. A.
AU - Leiden, J. M.
AU - Solaro, R. J.
PY - 2000
Y1 - 2000
N2 - 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.
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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M3 - Article
VL - 526
SP - 541
EP - 549
JO - Journal of Physiology
JF - Journal of Physiology
SN - 0022-3751
IS - 3
ER -