Endogenous nitric oxide mechanisms mediate the stretch dependence of Ca2+ release in cardiomyocytes
Endogenous nitric oxide mechanisms mediate the stretch dependence of Ca2+ release in cardiomyocytes
复制标题
DOI：
10.1038/ncb1001-867
复制
发表时间：
2001-10-01
影响因子：
21.3
通讯作者：
Sollott, SJ
中科院分区：
文献类型：
--
作者：
Petroff, MGV;Kim, SH;Sollott, SJ
心肌的拉伸通过增强Ca2+瞬态来调节收缩，但这是如何发生的仍不清楚。我们发现肌细胞的拉伸调节基本的Ca2+释放过程从红素受体Ca2+释放通道（RyRCs）， Ca2+火花和电刺激的Ca2+瞬态。拉伸诱导PtdIns-3-OH激酶（PI(3)K）依赖性磷酸化Akt和内皮型一氧化氮合酶（NOS），产生一氧化氮（NO），并通过抑制NOS和PI(3)K来消除Ca2+火花频率的比例增加。外源产生的NO可逆地增加Ca2+火花频率而不拉伸细胞。我们提出PI(3) k - akt -内皮细胞NOS轴激活产生的肌细胞NO通过增强RyRC活性作为拉伸的第二信使，促进心肌收缩激活。
Stretching of cardiac muscle modulates contraction through the enhancement of the Ca2+ transient, but how this occurs is still not known. We found that stretching of myocytes modulates the elementary Ca2+ release process from ryanodine-receptor Ca2+-release channels (RyRCs), Ca2+ sparks and the electrically stimulated Ca2+ transient. Stretching induces PtdIns-3-OH kinase (PI(3)K)-dependent phosphorylation of both Akt and the endothelial isoform of nitric oxide synthase (NOS), nitric oxide (NO) production, and a proportionate increase in Ca2+-spark frequency that is abolished by inhibiting NOS and PI(3)K. Exogenously generated NO reversibly increases Ca2+-spark frequency without cell stretching. We propose that myocyte NO produced by activation of the PI(3)K-Akt-endothelial NOS axis acts as a second messenger of stretch by enhancing RyRC activity, contributing to myocardial contractile activation.