Ca2+ Activation of Smooth Muscle Contraction
Ca2+ Activation of Smooth Muscle Contraction
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Ca2 激活平滑肌收缩
DOI：
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发表时间：
2002
影响因子：
4.8
通讯作者：
M. Walsh
中科院分区：
文献类型：
--
作者：
David P. Wilson;C. Sutherland;M. Walsh
平滑肌收缩是由钙/钙调蛋白（CaM）依赖性肌球蛋白轻链激酶（MLCK）催化的肌球蛋白20-kDa轻链磷酸化激活的。根据目前流行的理论，参与MLCK调节的CaM是无Ca 2+的，并且在静息胞质游离Ca 2+浓度（[Ca 2 +] i）下与激酶解离。[Ca 2 +] i的增加使CaM的四个Ca 2+结合位点饱和，然后结合并激活肌动蛋白结合的MLCK。本研究的结果表明，这一理论需要修订。在EGTA存在下，大鼠尾动脉平滑肌剥皮（脱膜）后保留了足够的CaM，以支持Ca 2+诱发的收缩，如先前在其他平滑肌组织中观察到的那样。这种紧密结合的钙调素被释放的钙调素拮抗剂三氟拉嗪（TFP）在Ca 2+的存在下。在去除（Ca 2+）4-CaM-TFP 2复合物后，Ca 2+不再诱导收缩。在收缩的[Ca 2 +]亚阈值下或甚至在没有Ca 2+的情况下（存在5 mm EGTA），将外源性CaM加入到经TMP处理的组织中，然后洗脱未结合的CaM，恢复了Ca 2+诱导的收缩;这需要MLCK激活，因为它被MLCK抑制剂ML-9阻断。因此，这些数据表明，一个特定的池的细胞钙调素，紧密结合到肌丝在休息[Ca 2 +] i，或甚至在没有Ca 2+，负责激活收缩后，局部增加[Ca 2 +]。这种机制将允许在远离肌丝的细胞区域中局部改变[Ca 2 +]，以调节不同的Ca 2+依赖性过程，而不触发收缩反应。因此，固定化的钙调素类似于肌钙蛋白C，横纹肌的钙结合调节蛋白，其也以钙非依赖性方式与细丝结合。
Smooth muscle contraction is activated by phosphorylation of the 20-kDa light chains of myosin catalyzed by Ca2+/calmodulin (CaM)-dependent myosin light chain kinase (MLCK). According to popular current theory, the CaM involved in MLCK regulation is Ca2+-free and dissociated from the kinase at resting cytosolic free Ca2+concentration ([Ca2+] i ). An increase in [Ca2+] i saturates the four Ca2+-binding sites of CaM, which then binds to and activates actin-bound MLCK. The results of this study indicate that this theory requires revision. Sufficient CaM was retained after skinning (demembranation) of rat tail arterial smooth muscle in the presence of EGTA to support Ca2+-evoked contraction, as observed previously with other smooth muscle tissues. This tightly bound CaM was released by the CaM antagonist trifluoperazine (TFP) in the presence of Ca2+. Following removal of the (Ca2+)4-CaM-TFP2 complex, Ca2+ no longer induced contraction. The addition of exogenous CaM to TFP-treated tissue at a [Ca2+] subthreshold for contraction or even in the absence of Ca2+(presence of 5 mm EGTA), followed by washout of unbound CaM, restored Ca2+-induced contraction; this required MLCK activation, since it was blocked by the MLCK inhibitor ML-9. The data suggest, therefore, that a specific pool of cellular CaM, tightly bound to myofilaments at resting [Ca2+] i , or even in the absence of Ca2+, is responsible for activation of contraction following a local increase in [Ca2+]. This mechanism would allow for localized changes in [Ca2+] in regions of the cell distant from the myofilaments to regulate distinct Ca2+-dependent processes without triggering a contractile response. Immobilized CaM, therefore, resembles troponin C, the Ca2+-binding regulatory protein of striated muscle, which is also bound to the thin filament in a Ca2+-independent manner.
DOI：
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发表时间：
1993-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
M. Kolodney;Elliot L. Elson
通讯作者：
M. Kolodney;Elliot L. Elson
单个平滑肌细胞收缩背后钙的区域变化。
DOI：
10.1126/science.3103219
发表时间：
1987
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Williams,DA;Becker,PL;Fay,FS
通讯作者：
Fay,FS