Redox modulation of L-type calcium channels in ferret ventricular myocytes. Dual mechanism regulation by nitric oxide and S-nitrosothiols.
Redox modulation of L-type calcium channels in ferret ventricular myocytes. Dual mechanism regulation by nitric oxide and S-nitrosothiols.
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DOI：
10.1085/jgp.108.4.277
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发表时间：
1996-10
期刊：
影响因子：
--
通讯作者：
Strauss HC
中科院分区：
文献类型：
--
作者：
Campbell DL;Stamler JS;Strauss HC
应用膜片钳技术研究了雪貂右心室肌细胞一氧化氮（NO）相关活性和细胞巯基氧化还原状态对L型钙电流（伊卡，L）的影响。SIN-1同时产生NO和O2-，对伊卡、L.在超氧化物歧化酶的存在下，只看到抑制。8-Br-cGMP对伊卡，L也有抑制作用，提示NO的抑制作用是cGMP依赖的.另一方面，S-亚硝基硫醇（RSNOs），提供NO+，刺激伊卡，L。RSNO的作用不依赖于细胞通透性，SR钙释放的调制，激酶的激活，磷酸酶的抑制，或cGMP水平的改变。通过巯基氧化剂对伊卡，L的类似激活，以及巯基还原剂的逆转，确定了L型钙通道亚基复合物上的变构巯基“氧化还原开关”，通过该氧化还原开关，NO/O2-和NO+转移可以发挥与NO产生的效果相反的效果。（a）间接（cGMP依赖性）和直接（S-亚硝基化/氧化）调节心室伊卡，L;（B）肌膜巯基氧化还原状态可能是伊卡，L活性的重要决定因素。
The effects of NO-related activity and cellular thiol redox state on basal L-type calcium current, ICa,L, in ferret right ventricular myocytes were studied using the patch clamp technique. SIN-1, which generates both NO. and O2-, either inhibited or stimulated ICa,L. In the presence of superoxide dismutase only inhibition was seen. 8-Br- cGMP also inhibited ICa,L, suggesting that the NO inhibition is cGMP- dependent. On the other hand, S-nitrosothiols (RSNOs), which donate NO+, stimulated ICa,L. RSNO effects were not dependent upon cell permeability, modulation of SR Ca2+ release, activation of kinases, inhibition of phosphatases, or alterations in cGMP levels. Similar activation of ICa,L by thiol oxidants, and reversal by thiol reductants, identifies an allosteric thiol-containing "redox switch" on the L-type calcium channel subunit complex by which NO/O2- and NO+ transfer can exert effects opposite to those produced by NO. In sum, our results suggest that: (a) both indirect (cGMP-dependent) and direct (S-nitrosylation/oxidation) regulation of ventricular ICa,L, and (b) sarcolemma thiol redox state may be an important determinant of ICa,L activity.