The R21C Mutation in Cardiac Troponin I Imposes Differences in Contractile Force Generation between the Left and Right Ventricles of Knock-In Mice
We investigated the effect of the hypertrophic cardiomyopathy-linked R21C (arginine to cysteine) mutation in human cardiac troponin I (cTnI) on the contractile properties and myofilament protein phosphorylation in papillary muscle preparations from left (LV) and right (RV) ventricles of homozygous R...
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doaj-0b6510a1eb454eea9038d905eceed7e72020-11-24T21:11:07ZengHindawi LimitedBioMed Research International2314-61332314-61412015-01-01201510.1155/2015/742536742536The R21C Mutation in Cardiac Troponin I Imposes Differences in Contractile Force Generation between the Left and Right Ventricles of Knock-In MiceJingsheng Liang0Katarzyna Kazmierczak1Ana I. Rojas2Yingcai Wang3Danuta Szczesna-Cordary4Department of Molecular & Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, USADepartment of Molecular & Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, USADepartment of Molecular & Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, USADepartment of Molecular & Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, USADepartment of Molecular & Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, USAWe investigated the effect of the hypertrophic cardiomyopathy-linked R21C (arginine to cysteine) mutation in human cardiac troponin I (cTnI) on the contractile properties and myofilament protein phosphorylation in papillary muscle preparations from left (LV) and right (RV) ventricles of homozygous R21C+/+ knock-in mice. The maximal steady-state force was significantly reduced in skinned papillary muscle strips from the LV compared to RV, with the latter displaying the level of force observed in LV or RV from wild-type (WT) mice. There were no differences in the Ca2+ sensitivity between the RV and LV of R21C+/+ mice; however, the Ca2+ sensitivity of force was higher in RV-R21C+/+ compared with RV-WT and lower in LV- R21C+/+ compared with LV-WT. We also observed partial loss of Ca2+ regulation at low [Ca2+]. In addition, R21C+/+-KI hearts showed no Ser23/24-cTnI phosphorylation compared to LV or RV of WT mice. However, phosphorylation of the myosin regulatory light chain (RLC) was significantly higher in the RV versus LV of R21C+/+ mice and versus LV and RV of WT mice. The difference in RLC phosphorylation between the ventricles of R21C+/+ mice likely contributes to observed differences in contractile force and the lower tension monitored in the LV of HCM mice.http://dx.doi.org/10.1155/2015/742536 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jingsheng Liang Katarzyna Kazmierczak Ana I. Rojas Yingcai Wang Danuta Szczesna-Cordary |
spellingShingle |
Jingsheng Liang Katarzyna Kazmierczak Ana I. Rojas Yingcai Wang Danuta Szczesna-Cordary The R21C Mutation in Cardiac Troponin I Imposes Differences in Contractile Force Generation between the Left and Right Ventricles of Knock-In Mice BioMed Research International |
author_facet |
Jingsheng Liang Katarzyna Kazmierczak Ana I. Rojas Yingcai Wang Danuta Szczesna-Cordary |
author_sort |
Jingsheng Liang |
title |
The R21C Mutation in Cardiac Troponin I Imposes Differences in Contractile Force Generation between the Left and Right Ventricles of Knock-In Mice |
title_short |
The R21C Mutation in Cardiac Troponin I Imposes Differences in Contractile Force Generation between the Left and Right Ventricles of Knock-In Mice |
title_full |
The R21C Mutation in Cardiac Troponin I Imposes Differences in Contractile Force Generation between the Left and Right Ventricles of Knock-In Mice |
title_fullStr |
The R21C Mutation in Cardiac Troponin I Imposes Differences in Contractile Force Generation between the Left and Right Ventricles of Knock-In Mice |
title_full_unstemmed |
The R21C Mutation in Cardiac Troponin I Imposes Differences in Contractile Force Generation between the Left and Right Ventricles of Knock-In Mice |
title_sort |
r21c mutation in cardiac troponin i imposes differences in contractile force generation between the left and right ventricles of knock-in mice |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2015-01-01 |
description |
We investigated the effect of the hypertrophic cardiomyopathy-linked R21C (arginine to cysteine) mutation in human cardiac troponin I (cTnI) on the contractile properties and myofilament protein phosphorylation in papillary muscle preparations from left (LV) and right (RV) ventricles of homozygous R21C+/+ knock-in mice. The maximal steady-state force was significantly reduced in skinned papillary muscle strips from the LV compared to RV, with the latter displaying the level of force observed in LV or RV from wild-type (WT) mice. There were no differences in the Ca2+ sensitivity between the RV and LV of R21C+/+ mice; however, the Ca2+ sensitivity of force was higher in RV-R21C+/+ compared with RV-WT and lower in LV- R21C+/+ compared with LV-WT. We also observed partial loss of Ca2+ regulation at low [Ca2+]. In addition, R21C+/+-KI hearts showed no Ser23/24-cTnI phosphorylation compared to LV or RV of WT mice. However, phosphorylation of the myosin regulatory light chain (RLC) was significantly higher in the RV versus LV of R21C+/+ mice and versus LV and RV of WT mice. The difference in RLC phosphorylation between the ventricles of R21C+/+ mice likely contributes to observed differences in contractile force and the lower tension monitored in the LV of HCM mice. |
url |
http://dx.doi.org/10.1155/2015/742536 |
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