Pharmacological and electrophysiological characterization of the human bile acid-sensitive ion channel (hBASIC)

Pharmacological and electrophysiological characterization of the human bile acid-sensitive ion channel (hBASIC)
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人胆汁酸敏感离子通道 (hBASIC) 的药理学和电生理学表征

DOI:
10.1007/s00424-013-1310-4
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发表时间:
2013
期刊:
Pflügers Archiv - European Journal of Physiology
影响因子:
--
通讯作者:
Wiemuth
Wiemuth
中科院分区:
--
文献类型:
--
作者:
Lefèvre;Diakov;Haerteis;Korbmacher;Gründer;Wiemuth

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人胆汁酸敏感离子通道(HBASIC)是退行性变/上皮性Na+通道基因家族中的一种阳离子通道,表达于肠道,可被胆汁酸激活。在这里,我们表明,除了它对胆汁酸的敏感性,hBASIC与它的大鼠同源基因有更多的关键特征:它被细胞外二价阳离子阻断,被微摩尔浓度的二芳胺基丁二氮烯抑制,并被毫摩尔浓度的氟芬那酸激活。此外,我们证明了人类胆汁中存在的两种主要胆汁酸,鹅去氧胆酸和脱氧胆酸,以协同方式激活hBASIC。此外,我们在外向式膜片钳记录中测试了hBASIC的单通道特性,显示出约11ps的单通道电导和高的Na+选择性。在膜片钳记录中,脱氧胆酸主要通过减少单通道关闭时间来激活hBASIC。综上所述,我们对hBASIC进行了全面的功能表征。
The human bile acid-sensitive ion channel (hBASIC) is a cation channel of the degenerin/epithelial Na+channel gene family that is expressed in the intestinal tract and can be activated by bile acids. Here, we show that in addition to its sensitivity for bile acids, hBASIC shares further key features with its rat ortholog: it is blocked by extracellular divalent cations, is inhibited by micromolar concentrations of the diarylamidine diminazene, and activated by millimolar concentrations of flufenamic acid. Furthermore, we demonstrate that two major bile acids present in human bile, chenodeoxycholic acid and deoxycholic acid, activate hBASIC in a synergistic manner. In addition, we determined the single-channel properties of hBASIC in outside-out patch clamp recordings, revealing a single-channel conductance of about 11 pS and a high Na+selectivity. Deoxycholic acid activates hBASIC in patch clamp recordings mainly by reducing the single-channel closed time. In summary, we provide a thorough functional characterization of hBASIC.
DOI: 10.1124/mol.111.073726
发表时间: 2011-11-01
影响因子: 3.6
作者:
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DOI: --
发表时间: 2010
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影响因子: --
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发表时间: 2012-10-01
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影响因子: 4.8
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DOI: 10.4161/chan.22406
发表时间: 2013-01-01
期刊: Channels (Austin, Tex.)
影响因子: --
作者:
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通讯作者: Gründer S