Hydrolyzable ATP and PIP(2) modulate the small-conductance K+ channel in apical membranes of rat cortical-collecting duct (CCD).
Hydrolyzable ATP and PIP(2) modulate the small-conductance K+ channel in apical membranes of rat cortical-collecting duct (CCD).
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可水解 ATP 和 PIP(2) 调节大鼠皮质集合管 (CCD) 顶膜中的小电导 K 通道。
DOI：
10.1085/jgp.20028677
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Giebisch,Gerhard
中科院分区：
文献类型：
--
作者：
Lu,Ming;Hebert,StevenC;Giebisch,Gerhard
皮质集合管（CCD）顶膜小电导钾通道（SK）受三磷酸腺苷（ATP）和磷酸化-去磷酸化过程的调节。当在异种卵母细胞中表达时，ROMK（一种类似于天然SK通道的克隆的K+通道）可以被磷脂酰肌醇二磷酸（PIP 2）刺激，所述PIP 2由磷脂酰肌醇产生的磷酸肌醇激酶产生。然而，PIP 2对SK通道活性的影响尚不清楚。在本研究中，我们调查的机制，水解ATP防止跑下来的SK通道活动在离体大鼠CCD的主细胞的顶端补丁。用可水解的Mg-ATP预处理可显著延缓通道的下降，而ATPγS和AMP-PNP则无此作用。碱性磷酸酶的加入也导致通道活性的丧失。在耗尽后，SK通道活性在加入PIP 2后迅速增加。暴露于磷酸肌醇激酶抑制剂（LY 294002，槲皮素或wortmannin）的内翻补丁减少通道活性的74%，在镁ATP的存在下。在这些磷酸肌醇激酶抑制剂的存在下，将PIP 2添加到切除的斑块中重新激活SK通道。蛋白激酶A抑制剂PKI在Mg-ATP存在下使通道活性降低36%。PIP 2还被证明可以调节细胞外和胞浆ATP的抑制作用。我们的结论是，ATP依赖性形成的PIP 2通过膜结合的磷酸肌醇激酶和磷酸激酶A的磷酸化的SK在调节SK通道的活动中发挥重要作用。
The small-conductance K+channel (SK) in the apical membrane of the cortical-collecting duct (CCD) is regulated by adenosine triphosphate (ATP) and phosphorylation-dephosphorylation processes. When expressed inXenopusoocytes, ROMK, a cloned K+channel similar to the native SK channel, can be stimulated by phosphatidylinositol bisphosphate (PIP2), which is produced by phosphoinositide kinases from phosphatidylinositol. However, the effects of PIP2on SK channel activity are not known. In the present study, we investigated the mechanism by which hydrolyzable ATP prevented run-down of SK channel activity in excised apical patches of principal cells from rat CCD. Channel run-down was significantly delayed by pretreatment with hydrolyzable Mg-ATP, but ATPγS and AMP-PNP had no effect. Addition of alkaline phosphatase also resulted in loss of channel activity. After run-down, SK channel activity rapidly increased upon addition of PIP2. Exposure of inside-out patches to phosphoinositide kinase inhibitors (LY294002, quercetin or wortmannin) decreased channel activity by 74% in the presence of Mg-ATP. PIP2added to excised patches reactivated SK channels in the presence of these phosphoinositide kinase inhibitors. The protein kinase A inhibitor, PKI, reduced channel activity by 36% in the presence of Mg-ATP. PIP2was also shown to modulate the inhibitory effects of extracellular and cytosolic ATP. We conclude that both ATP-dependent formation of PIP2through membrane-bound phosphoinositide kinases and phosphorylation of SK by PKA play important roles in modulating SK channel activity.
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弹性蛋白：蛋白质和基因结构与疾病的关系。
DOI：
--
发表时间：
1984
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
Rosenbloom,J
通讯作者：
Rosenbloom,J
DOI：
--
发表时间：
1989-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
M. Bashir;Z. Indik;H. Yeh;N. Ornstein-Goldstein;J. Rosenbloom;W. Abrams;M. Fazio;J. Uitto;J. Rosenbloom
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M. Bashir;Z. Indik;H. Yeh;N. Ornstein-Goldstein;J. Rosenbloom;W. Abrams;M. Fazio;J. Uitto;J. Rosenbloom
DOI：
10.1016/b978-0-12-363708-6.50010-2
发表时间：
1979
期刊：
International review of connective tissue research
影响因子：
--
作者：
Janice M. Burke;J. Burke;R. Ross;R. Ross
通讯作者：
R. Ross
从人类粘粒文库中分离β-珠蛋白相关基因。
DOI：
--
发表时间：
1981
期刊：
影响因子：
--
作者：
F. Grosveld;H. Dahl;E. Boer;R. Flavell
通讯作者：
R. Flavell
DOI：
10.1073/pnas.84.16.5680
发表时间：
1987-08-01
影响因子：
11.1
作者：
INDIK, Z;YEH, H;ROSENBLOOM, J
通讯作者：
ROSENBLOOM, J