Inhibition by protein kinase C of the KNDP subtype of vascular smooth muscle ATP-sensitive potassium channel
Inhibition by protein kinase C of the KNDP subtype of vascular smooth muscle ATP-sensitive potassium channel
复制标题
DOI：
10.1161/01.res.87.2.112
复制
发表时间：
2000-07-21
影响因子：
20.1
通讯作者：
Light, PE
中科院分区：
文献类型：
--
作者：
Cole, WC;Malcolm, T;Light, PE
atp敏感的K+通道（K- atp）参与血管平滑肌细胞的张力调节。我们确定了蛋白激酶C （PKC）激活对血管平滑肌K-ATP通道核苷二磷酸激活（K-NDP）亚型的影响。Phorbol 12,13-二丁酸酯（PdBu）和血管紧张素II抑制兔门静脉（PV）肌细胞C-A斑块的KNDP活性，但无活性Phorbol酯对其无影响，PKC抑制剂预处理可阻止PdBu的作用。组成活性PKC抑制I-O斑块中的K-NDP，但在PKC的特异性肽抑制剂存在时没有作用。PdBu增加了长时间的爆发间闭合状态的持续时间，但对爆发持续时间和爆发内动力学没有影响，PdBu抑制了大鼠PV的K-NDP，但对70-pS K-ATP通道没有影响。结果表明，PKC的激活可抑制血管平滑肌K-ATP通道的K-NDP亚型。因此，通过涉及PKC的细胞内信号级联控制K-NDP活性可能有助于血管收缩剂控制张力和动脉直径。
ATP-sensitive K+ channels (K-ATP) contribute to the regulation of tone in vascular smooth muscle cells. We determined the effects of protein kinase C (PKC) activation on the nucleoside diphosphate-activated (K-NDP) subtype of vascular smooth muscle K-ATP channel. Phorbol 12,13-dibutyrate (PdBu) and angiotensin II inhibited KNDP activity Of C-A patches of rabbit portal vein (PV) myocytes, but an inactive phorbol ester was without effect, and pretreatment with PKC inhibitor prevented the actions of PdBu. Constitutively active PKC inhibited K-NDP in I-O patches but was without effect in the presence of a specific peptide inhibitor of PKC. PdBu increased the duration of a long-lived interburst closed state but was without effect on burst duration or intraburst kinetics, PdBu treatment inhibited K-NDP, but not a 70-pS K-ATP channel of rat PV. The results indicate that the K-NDP subtype of vascular smooth muscle K-ATP channel is inhibited by activation of PKC. Control of K-NDP activity by intracellular signaling cascades involving PKC may, therefore, contribute to control of tone and arterial diameter by vasoconstrictors.