Regulation of a Human Chloride Channel

Regulation of a Human Chloride Channel
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人氯通道的调节

DOI:
--
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发表时间:
2001
影响因子:
4.8
通讯作者:
S. Shears
S. Shears
中科院分区:
生物学2区
文献类型:
--
作者:
M. Ho;M. Kaetzel;D. Armstrong;S. Shears

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我们研究了人胰腺癌上皮细胞系(CFPAC-1)中不表达功能性cAMP依赖的囊性纤维化跨膜电导调节因子氯通道的钙依赖氯通道的调节。在这些细胞的无细胞斑块中,生理钙离子浓度激活了单一类别的1-Picosiemens CL-−选择性通道。同样的通道也被纯化的II型钙调蛋白依赖的蛋白激酶(CaMKII)刺激,并在细胞附着的斑块中被嘌呤能激动剂刺激。在全细胞记录中,Ca~(2+)依赖和CaMKII依赖的机制都有助于Ca~(2+)对氯通道的刺激,但CaMKII依赖的通路可被肌醇3,4,5,6-四氢磷酸肌醇(Ins(3,4,5,6)P4)选择性地抑制。Ins(3,4,5,6)P4对CaMKII刺激ClCachanels的抑制作用可通过升高[Ca~(2+)]而减弱,并可被100 nm冈田酸抑制蛋白磷酸酶活性所阻断。这些数据为理解Ins(3,4,5,6)P4在调节上皮细胞钙依赖的Cl-−通量中的生理学意义提供了新的背景。
We have studied the regulation of Ca2+-dependent chloride (ClCa) channels in a human pancreatoma epithelial cell line (CFPAC-1), which does not express functional cAMP-dependent cystic fibrosis transmembrane conductance regulator chloride channels. In cell-free patches from these cells, physiological Ca2+ concentrations activated a single class of 1-picosiemens Cl−-selective channels. The same channels were also stimulated by a purified type II calmodulin-dependent protein kinase (CaMKII), and in cell-attached patches by purinergic agonists. In whole-cell recordings, both Ca2+- and CaMKII-dependent mechanisms contributed to chloride channel stimulation by Ca2+, but the CaMKII-dependent pathway was selectively inhibited by inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P4). This inhibitory effect of Ins(3,4,5,6)P4 on ClCachannel stimulation by CaMKII was reduced by raising [Ca2+] and prevented by inhibition of protein phosphatase activity with 100 nm okadaic acid. These data provide a new context for understanding the physiological relevance of Ins(3,4,5,6)P4 in the longer term regulation of Ca2+-dependent Cl− fluxes in epithelial cells.
DOI: 10.1126/science.279.5348.227
发表时间: 1998-01-09
期刊: SCIENCE
影响因子: 56.9
作者:
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DOI: --
发表时间: 1994
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期刊: American journal of physiology. Cell physiology
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DOI: --
发表时间: 1994
期刊: The Journal of biological chemistry
影响因子: --
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发表时间: 1996-09-17
影响因子: 11.1
作者:
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通讯作者: Barrett, KE