The R21C mutation in cardiac troponin i imposes differences in contractile force generation between the left and right ventricles of knock-in mice

Jingsheng Liang, Katarzyna Kazmierczak, Ana I. Rojas, Yingcai Wang, Danuta Szczesna-Cordary

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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<sup>+/+</sup> 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 Ca<sup>2+</sup> sensitivity between the RV and LV of R21C<sup>+/+</sup> mice; however, the Ca<sup>2+</sup> sensitivity of force was higher in RV-R21C<sup>+/+</sup> compared with RV-WT and lower in LV-R21C<sup>+/+</sup> compared with LV-WT. We also observed partial loss of Ca<sup>2+</sup> regulation at low [Ca<sup>2+</sup>]. In addition, R21C<sup>+/+</sup>-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<sup>+/+</sup> mice and versus LV and RV of WT mice. The difference in RLC phosphorylation between the ventricles of R21C<sup>+/+</sup> mice likely contributes to observed differences in contractile force and the lower tension monitored in the LV of HCM mice.

Original languageEnglish (US)
Article number742536
JournalBioMed Research International
Volume2015
DOIs
StatePublished - 2015

Fingerprint

Phosphorylation
Troponin
Heart Ventricles
Mutation
Troponin I
Muscle
Myosin Light Chains
Papillary Muscles
Cysteine
Arginine
Myofibrils
Hypertrophic Cardiomyopathy
Proteins
Light

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

@article{b4376b0611b240598e4033f2b19ccb8a,
title = "The R21C mutation in cardiac troponin i imposes differences in contractile force generation between the left and right ventricles of knock-in mice",
abstract = "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.",
author = "Jingsheng Liang and Katarzyna Kazmierczak and Rojas, {Ana I.} and Yingcai Wang and Danuta Szczesna-Cordary",
year = "2015",
doi = "10.1155/2015/742536",
language = "English (US)",
volume = "2015",
journal = "BioMed Research International",
issn = "2314-6133",
publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - The R21C mutation in cardiac troponin i imposes differences in contractile force generation between the left and right ventricles of knock-in mice

AU - Liang, Jingsheng

AU - Kazmierczak, Katarzyna

AU - Rojas, Ana I.

AU - Wang, Yingcai

AU - Szczesna-Cordary, Danuta

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84928966496&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928966496&partnerID=8YFLogxK

U2 - 10.1155/2015/742536

DO - 10.1155/2015/742536

M3 - Article

C2 - 25961037

AN - SCOPUS:84928966496

VL - 2015

JO - BioMed Research International

JF - BioMed Research International

SN - 2314-6133

M1 - 742536

ER -