Dual effect of insulin-like growth factor on the apical 70-pS K channel in the thick ascending limb of rat kidney.

Dual effect of insulin-like growth factor on the apical 70-pS K channel in the thick ascending limb of rat kidney.
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胰岛素样生长因子对大鼠肾升肢粗段顶端 70-pS K 通道的双重作用。

DOI:
10.1152/ajpcell.00441.2003
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发表时间:
2004
期刊:
American journal of physiology. Cell physiology
影响因子:
--
通讯作者:
Wang,Wen-Hui
Wang,Wen-Hui
中科院分区:
--
文献类型:
--
作者:
Wei,Yuan;Chen,Yu-Jung;Li,Dimin;Gu,Ruimin;Wang,Wen-Hui

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用膜片钳技术研究胰岛素样生长因子-I(IGF-I)对大鼠肾脏粗大升支(TAL)心尖70-pS钾通道的影响。分离的TAL被切开以进入根尖膜。添加25 nM IGF-I刺激心尖70-pS K通道,并使通道活动性从0.31增加到1.21,通道活动性由通道开放概率和通道数量的乘积定义。IGF-I的刺激作用不是通过一氧化氮或蛋白酪氨酸磷酸酶依赖的机制实现的,因为抑制一氧化氮合酶或阻断蛋白酪氨酸磷酸酶并不能消除IGF-I对70-pS钾通道的刺激作用。相反,用PD-98059或U0126抑制丝裂原活化蛋白(MAP)激酶可消除胰岛素样生长因子-I的刺激作用。提示MAPK参与了IGF-I对心尖K通道的调节作用。此外,IGF-I对心尖70-pS钾通道的作用是双相的,因为高浓度(200 NM)抑制心尖70-pS K通道。应用400 nM IGF-I可使通道活动从1.45降至0.2。PKC抑制剂Calphostin C不能阻断IGF-I的抑制作用,但用除草剂Hbimycin A抑制蛋白酪氨酸激酶可取消IGF的抑制作用。我们认为IGF-I对TAL顶端70-pS钾通道具有双重作用:低浓度的IGF-I刺激,高浓度的IGF-I抑制通道活动。IGF-I的刺激作用是通过MAP依赖的途径介导的,而抑制作用则是蛋白酪氨酸激酶刺激的结果。
We used the patch-clamp technique to study the effect of insulin-like growth factor I (IGF-I) on the apical 70-pS K channel in the isolated thick ascending limb (TAL) of the rat kidney. The isolated TAL was cut open to gain access to the apical membrane. Addition of 25 nM IGF-I stimulates the apical 70-pS K channel and increases channel activity, defined by the product of channel open probability and channel number, from 0.31 to 1.21. The stimulatory effect of IGF-I is not mediated by nitric oxide- or protein tyrosine phosphatase-dependent mechanisms, because inhibition of nitric oxide synthase or blocking protein tyrosine phosphatase did not abolish the stimulatory effect of IGF-I on the 70-pS K channel. In contrast, inhibition of mitogen-activated protein (MAP) kinase with PD-98059 or U0126 abolished the stimulatory effect of IGF-I. This suggests that MAP kinase is responsible for mediating the effect of IGF-I on the apical K channels. Moreover, the effect of IGF-I on the apical 70-pS K channel is biphasic because high concentrations (>200 nM) inhibit apical 70-pS K channels. Application of 400 nM IGF-I decreased channel activity from 1.45 to 0.2. The inhibitory effect of IGF-I is not blocked by calphostin C (an inhibitor of PKC), but inhibition of protein tyrosine kinase with herbimycin A abolished the IGF-induced inhibition. We conclude that IGF-I has a dual effect on the apical 70-pS K channel in the TAL: low concentrations of IGF-I stimulate, whereas high concentrations inhibit the channel activity. The stimulatory effect of IGF-I is mediated by a MAP kinase-dependent pathway, whereas the inhibitory effect is the result of stimulation of protein tyrosine kinase.
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