R21C Mutation in Cardiac Troponin I Imposes Differences in the Degree of Order and Kinetics of Myosin Cross-Bridges of Left and Right Ventricles
In: Biophysical Journal, Jg. 108 (2015), S. 293a
Online
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Zugriff:
The effect of the TnI R21C mutation in the human cardiac troponin I, the mutation that is linked to hypertrophic cardiomyopathy, on muscles of the left (LV) and right (RV) ventricles was examined in the knock-in mice. Experiments were on a mesoscopic scale where the contribution of a single molecule makes difference to the overall signal. We examined 3-4 actin molecules in ex-vivo myofibrils prepared from LV and RV muscles. Experiments revealed that the mutation imposed significant differences in the distribution of actin angles: during contraction, actin from LV were much more tightly distributed compared to actin from RV. They also revealed that the mutation imposed significant difference on the kinetics cycle of cross-bridges (XBs) of the LV and RV: XBs from RV displayed a 3-fold decrease in the rate of power stroke and a 2-fold decrease in the rate of dissociation from thin filaments as compared to LV. We speculate that mutation operates differently in both ventricles because of the differences in external load between LV and RV. Kinetic results suggest that an increase in isometric tension observed in mutated RV results from an inability of XBs to dissociate promptly from thin filaments.
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R21C Mutation in Cardiac Troponin I Imposes Differences in the Degree of Order and Kinetics of Myosin Cross-Bridges of Left and Right Ventricles
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Autor/in / Beteiligte Person: | Rich, Ryan ; Raut, Sangram ; Borejdo, Julian ; Gryczynski, Zygmunt ; Das, Hriday K. ; Duggal, Divya ; Gryczynski, Ignacy ; Nagwekar, Janhavi ; Fudala, Rafal |
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Zeitschrift: | Biophysical Journal, Jg. 108 (2015), S. 293a |
Veröffentlichung: | Elsevier BV, 2015 |
Medientyp: | unknown |
ISSN: | 0006-3495 (print) |
DOI: | 10.1016/j.bpj.2014.11.1597 |
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