Protein kinase A-dependent modulation of Ca2+ sensitivity in cardiac and fast skeletal muscles after reconstitution with cardiac troponin.
Protein kinase A-dependent modulation of Ca2+ sensitivity in cardiac and fast skeletal muscles after reconstitution with cardiac troponin.
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DOI：
10.1085/jgp.200910206
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发表时间：
2009-06
期刊：
影响因子：
--
通讯作者：
Fukuda N
中科院分区：
文献类型：
--
作者：
Matsuba D;Terui T;O-Uchi J;Tanaka H;Ojima T;Ohtsuki I;Ishiwata S;Kurihara S;Fukuda N
蛋白激酶A （PKA）依赖性肌钙蛋白（Tn）I的磷酸化是心肌β-肾上腺素能刺激过程中通过削弱与TnC的相互作用来降低肌纤维Ca2+敏感性的主要生理机制。通过利用细丝重构，我们直接研究了pka依赖性的心肌TnI （cTnI）磷酸化是否会降低不同类型肌肉：心肌（猪心室）和快速骨骼肌（兔腰肌）的Ca2+敏感性。PKA增强了皮肤心肌中cTnI在Ser23/24处的磷酸化，降低了Ca2+敏感性，其作用在与心脏Tn复合物（cTn）或杂交Tn复合物（称为PCRF；快速骨骼TnT与cTnI和cTnC）重建后得到证实。快速骨骼Tn复合物（sTn）重构心肌不仅增加了Ca2+敏感性，而且消除了PKA的Ca2+脱敏作用，支持了cTnI的磷酸化，而不是其他肌原纤维蛋白（如肌球蛋白结合蛋白C）的磷酸化，主要是PKA诱导的心肌Ca2+脱敏的基础。用cTn重建快速骨骼肌降低Ca2+敏感性，PKA进一步降低Ca2+敏感性，随后用sTn重建后几乎完全恢复到原来的水平。当用PCRF重建快速骨骼肌时，获得了基本相同的结果。因此，这表明pka依赖的cTnI磷酸化或去磷酸化普遍调节与cTnC相关的横切肌肌节Ca2+敏感性，独立于TnT亚型。
Protein kinase A (PKA)-dependent phosphorylation of troponin (Tn)I represents a major physiological mechanism during β-adrenergic stimulation in myocardium for the reduction of myofibrillar Ca2+ sensitivity via weakening of the interaction with TnC. By taking advantage of thin filament reconstitution, we directly investigated whether or not PKA-dependent phosphorylation of cardiac TnI (cTnI) decreases Ca2+ sensitivity in different types of muscle: cardiac (porcine ventricular) and fast skeletal (rabbit psoas) muscles. PKA enhanced phosphorylation of cTnI at Ser23/24 in skinned cardiac muscle and decreased Ca2+ sensitivity, of which the effects were confirmed after reconstitution with the cardiac Tn complex (cTn) or the hybrid Tn complex (designated as PCRF; fast skeletal TnT with cTnI and cTnC). Reconstitution of cardiac muscle with the fast skeletal Tn complex (sTn) not only increased Ca2+ sensitivity, but also abolished the Ca2+-desensitizing effect of PKA, supporting the view that the phosphorylation of cTnI, but not that of other myofibrillar proteins, such as myosin-binding protein C, primarily underlies the PKA-induced Ca2+ desensitization in cardiac muscle. Reconstitution of fast skeletal muscle with cTn decreased Ca2+ sensitivity, and PKA further decreased Ca2+ sensitivity, which was almost completely restored to the original level upon subsequent reconstitution with sTn. The essentially same result was obtained when fast skeletal muscle was reconstituted with PCRF. It is therefore suggested that the PKA-dependent phosphorylation or dephosphorylation of cTnI universally modulates Ca2+ sensitivity associated with cTnC in the striated muscle sarcomere, independent of the TnT isoform.
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影响因子：
5.5
作者：
Fukuda, N;Wu, YM;Granzier, H
通讯作者：
Granzier, H
影响因子：
--
作者：
GUPTA, RC;NEUMANN, J;WATANABE, AM
通讯作者：
WATANABE, AM
影响因子：
4.8
作者：
NOLAND, TA;GUO, XD;KUO, JF
通讯作者：
KUO, JF
影响因子：
20.1
作者：
Cazorla, O;Freiburg, A;Granzier, H
通讯作者：
Granzier, H
TITIN的磷酸化可调节心脏肌肉的被动刚度，依赖性替丁同工型。
影响因子：
3.8
作者：
Fukuda, Norio;Wu, Yiming;Nair, Preetha;Granzier, Henk L
通讯作者：
Granzier, Henk L