278 Changes in cardiac troponin C (cTnC) calcium affinity induced by the familial hypertrophic cardiomyopathy-related mutation L29Q

2011 ◽  
Vol 27 (5) ◽  
pp. S162-S163
Author(s):  
A.Y. Li ◽  
B. Liang ◽  
W. Mudalige ◽  
G. Tibbits
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Cardiac Troponin ◽  
Troponin C ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Cardiac Troponin C ◽  
Calcium Affinity

Familial hypertrophic cardiomyopathy-related cardiac troponin C mutation L29Q affects Ca2+ binding and myofilament contractility

2008 ◽  
Vol 33 (2) ◽  
pp. 257-266 ◽  
Author(s):  
Bo Liang ◽  
Franca Chung ◽  
Yang Qu ◽  
Dmitri Pavlov ◽  
Todd E. Gillis ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Cardiac Myocytes ◽  
Cardiac Troponin ◽  
Sarcomere Length ◽  
Troponin C ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Force Generation ◽  
Binding Characteristics ◽  
Cardiac Troponin C ◽  
Myocyte Contractility

The cardiac troponin C (cTnC) mutation, L29Q, has been found in a patient with familial hypertrophic cardiomyopathy. We previously showed that L29, together with neighboring residues, Asp2, Val28, and Gly30, plays an important role in determining the Ca2+ affinity of site II, the regulatory site of mammalian cardiac troponin C (McTnC). Here we report on the Ca2+ binding characteristics of L29Q McTnC and D2N/V28I/L29Q/G30D McTnC (NIQD) utilizing the Phe27 → Trp (F27W) substitution, allowing one to monitor Ca2+ binding and release. We also studied the effect of these mutants on Ca2+ activation of force generation in single mouse cardiac myocytes using cTnC replacement, together with sarcomere length (SL) dependence. The Ca2+-binding affinity of site II of L29Q McTnCF27W and NIQD McTnCF27W was ∼1.3- and ∼1.9-fold higher, respectively, than that of McTnCF27W. The Ca2+ disassociation rate from site II of L29Q McTnCF27W and NIQD McTnCF27W was not significantly different than that of control (McTnCF27W). However, the rate of Ca2+ binding to site II was higher in L29Q McTnCF27W and NIQD McTnCF27W relative to control (∼1.5-fold and ∼2.0-fold respectively). The Ca2+ sensitivity of force generation was significantly higher in myocytes reconstituted with L29Q McTnC (∼1.4-fold) and NIQD McTnC (∼2-fold) compared with those reconstituted with McTnC. Interestingly, the change in Ca2+ sensitivity of force generation in response to an SL change (1.9, 2.1, and 2.3 μm) was significantly reduced in myocytes containing L29Q McTnC or NIQD McTnC. These results demonstrate that the L29Q mutation enhances the Ca2+-binding characteristics of cTnC and that when incorporated into cardiac myocytes, this mutant alters myocyte contractility.

scholarly journals Familial Hypertrophic Cardiomyopathy (FHC)-Related Cardiac Troponin C (cTnC) L29Q Mutation Alters the Contractility and the Functional Effects of the Phosphomimetric cTnI

2012 ◽  
Vol 102 (3) ◽  
pp. 358a
Author(s):  
Alison Y. Li ◽  
Bo Liang ◽  
Sean C. Little ◽  
Jonathan Davis ◽  
Glen F. Tibbits
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Cardiac Troponin ◽  
Troponin C ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Cardiac Troponin C

scholarly journals In Vitro and in Situ Structure and Function of the Cardiac Troponin C Familial Hypertrophic Cardiomyopathy-Linked Mutation, L29Q

2014 ◽  
Vol 106 (2) ◽  
pp. 723a-724a ◽  
Author(s):  
Ian M. Robertson ◽  
Ivanka Sevrieva ◽  
Monica X. Li ◽  
Malcolm Irving ◽  
Yin-Biao Sun ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Cardiac Troponin ◽  
Structure And Function ◽  
Troponin C ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Cardiac Troponin C ◽  
And Function

scholarly journals The structural and functional effects of the familial hypertrophic cardiomyopathy-linked cardiac troponin C mutation, L29Q

2015 ◽  
Vol 87 ◽  
pp. 257-269 ◽  
Author(s):  
Ian M. Robertson ◽  
Ivanka Sevrieva ◽  
Monica X. Li ◽  
Malcolm Irving ◽  
Yin-Biao Sun ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Cardiac Troponin ◽  
Troponin C ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Cardiac Troponin C

scholarly journals Familial Hypertrophic Cardiomyopathy Related Cardiac Troponin C L29Q Mutation Alters Length-Dependent Activation and Functional Effects of Phosphomimetic Troponin I*

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e79363 ◽  
Author(s):  
Alison Y. Li ◽  
Charles M. Stevens ◽  
Bo Liang ◽  
Kaveh Rayani ◽  
Sean Little ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin C ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Cardiac Troponin C ◽  
Length Dependent Activation

scholarly journals Hypertrophic Cardiomyopathy Cardiac Troponin C Mutations Differentially Affect Slow Skeletal and Cardiac Muscle Regulation

2017 ◽  
Vol 8 ◽  
Author(s):  
Tiago Veltri ◽  
Maicon Landim-Vieira ◽  
Michelle S. Parvatiyar ◽  
David Gonzalez-Martinez ◽  
Karissa M. Dieseldorff Jones ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Cardiac Muscle ◽  
Cardiac Troponin ◽  
Troponin C ◽  
Muscle Regulation ◽  
Cardiac Troponin C ◽  
Cardiac Muscle Regulation
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