Reis Stephanie, Littwitz Christoph, Preilowski Sebastian, Mügge Andreas, Stienen Ger J M, Pott Lutz, Jaquet Kornelia
Forschungslabor Molekulare Kardiologie, Bergmannsheil/St Josef-Hospital, Kliniken der Ruhr-Universität Bochum, Gudrunstr.56, 44791, Bochum, Germany.
Pflugers Arch. 2008 Oct;457(1):17-24. doi: 10.1007/s00424-008-0487-4. Epub 2008 Jun 12.
The R145G amino acid exchange in the inhibitory subunit (cTnI) of cardiac troponin, which regulates muscle contraction, is related to familial hypertrophic cardiomyopathy. Information on its impact on contractility of adult cardiomyocytes is scarce. We studied shortening of adult rat cardiomyocytes before and during ss-adrenergic stimulation using adenovirus-driven expression of human cTnI-wild type (wt) and cTnI-R145G. Baseline sarcomere shortening was significantly decreased by cTnI-R145G expression. Upon ss-adrenergic stimulation using isoproterenol (ISO), nearly identical amplitudes of shortening were obtained with cells expressing cTnI-R145G and control cardiomyocytes (native and cTnI-wt). However, rates of shortening and relengthening were depressed in cTnI-R145G-expressing cells but were comparable to those of control cells upon addition of forskolin or ISO and ICI118,551. This indicates that cTnI-R145G expression influences the response to ss-adrenergic stimulation dependent on the receptor subtype.
心肌肌钙蛋白抑制亚基（cTnI）中的R145G氨基酸交换与家族性肥厚型心肌病有关，该亚基调节肌肉收缩。关于其对成年心肌细胞收缩性影响的信息很少。我们使用腺病毒驱动的人cTnI野生型（wt）和cTnI-R145G表达，研究了成年大鼠心肌细胞在β-肾上腺素能刺激之前和期间的缩短情况。cTnI-R145G表达显著降低了基线肌节缩短。在用异丙肾上腺素（ISO）进行β-肾上腺素能刺激时，表达cTnI-R145G的细胞和对照心肌细胞（天然和cTnI-wt）获得了几乎相同的缩短幅度。然而，表达cTnI-R145G的细胞中缩短和再延长的速率降低，但在加入福斯可林或ISO以及ICI118,551后与对照细胞相当。这表明cTnI-R145G表达影响了依赖于受体亚型的对β-肾上腺素能刺激的反应。
