Functionally conservative substitutions at cardiac troponin I S43/45.

Abstract:

:A phospho-null Ala substitution at protein kinase C (PKC)-targeted cardiac troponin I (cTnI) S43/45 reduces myocyte and cardiac contractile function. The goal of the current study was to test whether cTnIS43/45N is an alternative, functionally conservative substitution in cardiac myocytes. Partial and more extensive endogenous cTnI replacement was similar at 2 and 4 days after gene transfer, respectively, for epitope-tagged cTnI and cTnIS43/45N. This replacement did not significantly change thin filament stoichiometry. In functional studies, there were no significant changes in the amplitude and/or rates of contractile shortening and re-lengthening after this partial (2 days) and extensive (4 days) replacement with cTnIS43/45N. The cTnIS43/45N substitution also was not associated with adaptive changes in the myocyte Ca(2+) transient or in phosphorylation of the protein kinase A and C-targeted cTnIS23/24 site. These results provide evidence that cTnIS43/45N is a functionally conservative substitution, and may be appropriate for use as a phospho-null in rodent models designed for studies on PKC modulation of cardiac performance.

journal_name

Arch Biochem Biophys

authors

Lang SE,Stevenson TK,Xu D,O'Connell R,Westfall MV

doi

10.1016/j.abb.2016.02.002

subject

Has Abstract

pub_date

2016-07-01 00:00:00

pages

42-7

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(16)30021-2

journal_volume

601

pub_type

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