Troponin T isoforms alter the tolerance of transgenic mouse cardiac muscle to acidosis

被引:17
|
作者
Nosek, TM
Brotto, MA
Jin, JP
机构
[1] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60201 USA
[2] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA
关键词
troponin T isoforms; cardiac muscle; pH; acidosis; transgenic mouse; contractility; Ca2+ sensitivity;
D O I
10.1016/j.abb.2004.07.014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Troponin T (TnT) is an essential protein in the Ca2+ regulatory system of striated of muscle. Three fiber type-specific TnT genes have evolved in higher vertebrates to encode cardiac, slow and fast skeletal muscle TnT isoforms. To understand the functional significance of TnT isoforms, we studied the effects of acidosis on the contractility of transgenic mouse cardiac muscle that expresses fast skeletal muscle TnT. Contractility analysis of intact cardiac muscle strips showed that while no differences were detected at physiological pH, the transgenic cardiac muscle had significantly greater decreases in +dF/dt(max) at acidic pH than that of the wild-type control. Contractility of skinned cardiac muscles demonstrated that the presence of fast TnT resulted in significantly larger decreases in force and Ca2+ sensitivity at acidic pH than that of the wild-type control. The effect of TnT isoforms on the tolerance of muscle to acidosis may explain the higher tolerance of embryonic versus adult cardiac muscles. The results are consistent with the hypothesis that charge differences in TnT isoforms contribute to the contractility of muscle. The data further support a hypothesis that slow TnT is similar to the cardiac, but not fast, and TnT may contribute to the higher tolerance of slow muscles to stress conditions. Therefore, TnT isoform diversity may contribute to the compatibility of muscle thin filaments to cellular environments in different fiber types, during development and functional adaptation. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:178 / 184
页数:7
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