Blebbistatin specifically inhibits actin-myosin interaction in mouse cardiac muscle
Blebbistatin specifically inhibits actin-myosin interaction in mouse cardiac muscle
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DOI：
10.1152/ajpcell.00551.2006
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发表时间：
2007-09-01
影响因子：
5.5
通讯作者：
Arner, Anders
中科院分区：
文献类型：
--
作者：
Dou, Ying;Arlock, Per;Arner, Anders
布莱比抗蛋白是孤立的收缩蛋白中肌动蛋白肌球蛋白相互作用的强大抑制剂。为了检查布尔比生蛋白是否在有组织的肌肉收缩系统中以类似的方式起作用，研究了布列比生蛋白对小鼠心脏组织收缩的影响。在微摩尔范围（1.3-2.8 mu M）的抑制常数（1.3-2.8 mu）的情况下，布莱比司汀抑制了节奏完整的乳头肌制剂的收缩和分离的心肌细胞的缩短。抑制常数类似于先前报道的孤立心脏肌球蛋白亚碎片的抑制常数，表明在心脏收缩仪的丝状肌球蛋白和分离的蛋白质中，泡蛋白的作用相似。抑制与动作电位持续时间的改变或通过L型Ca2+通道的流入减少无关。透化心肌制剂的实验表明，抑制并不是由于收缩丝的Ca2+灵敏度的改变。最大缩短速度不受1 mu m blebbistatin的影响。总之，我们表明，布莱比抗抑素是有组织的心肌收缩系统中肌动蛋白肌球蛋白相互作用的抑制剂，其作用并不是由于对CA2+涌入和激活系统的影响。
Blebbistatin is a powerful inhibitor of actin-myosin interaction in isolated contractile proteins. To examine whether blebbistatin acts in a similar manner in the organized contractile system of striated muscle, the effects of blebbistatin on contraction of cardiac tissue from mouse were studied. The contraction of paced intact papillary muscle preparations and shortening of isolated cardiomyocytes were inhibited by blebbistatin with inhibitory constants in the micromolar range (1.3-2.8 mu M). The inhibition constants are similar to those previously reported for isolated cardiac myosin subfragments showing that blebbistatin action is similar in filamentous myosin of the cardiac contractile apparatus and isolated proteins. The inhibition was not associated with alterations in action potential duration or decreased influx through L-type Ca2+ channels. Experiments on permeabilized cardiac muscle preparations showed that the inhibition was not due to alterations in Ca2+ sensitivity of the contractile filaments. The maximal shortening velocity was not affected by 1 mu M blebbistatin. In conclusion, we show that blebbistatin is an inhibitor of the actin-myosin interaction in the organized contractile system of cardiac muscle and that its action is not due to effects on the Ca2+ influx and activation systems.