Unexpected Down-regulation of the hIK1 Ca2+-activated K+ Channel by Its Opener 1-Ethyl-2-benzimidazolinone in HaCaT Keratinocytes
Unexpected Down-regulation of the hIK1 Ca2+-activated K+ Channel by Its Opener 1-Ethyl-2-benzimidazolinone in HaCaT Keratinocytes
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HaCaT 角质形成细胞中 hIK1 Ca2 激活 K 通道的开启子 1-乙基-2-苯并咪唑啉酮意外下调
DOI：
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发表时间：
2003
影响因子：
4.8
通讯作者：
C. Alzheimer
中科院分区：
文献类型：
--
作者：
Heidi Koegel;S. Kaesler;R. Burgstahler;S. Werner;C. Alzheimer
我们采用电生理和细胞和分子生物学技术相结合的研究中电导钙激活的K+通道，hIK 1，在HaCaT角质形成细胞的调节和功能作用。当我们将细胞与hIK 1开放剂1-乙基-2-苯并咪唑啉酮（1-EBIO）一起孵育以研究通道活性延长的细胞后果时，在几小时内发生了意想不到的通道下调。hIK 1开放剂chlorzoxazone和zoxazamine产生了相同的效果，并且在不同的细胞系（C6胶质瘤细胞）中也观察到了这种效果。用1-EBIO处理3天后，hIK 1的mRNA水平显著降低，并且未检测到通道活性。hIK 1的下调伴随着有丝分裂活性的丧失和细胞大小的强烈增加。撤除1-EBIO后，hIK 1 mRNA和通道活性完全恢复，细胞恢复促有丝分裂活性。我们的数据提供的证据表明，一种新的反馈机制的hIK 1的表达，似乎是由于其药理学激活剂在长期应用过程中的矛盾作用。由于hIK 1的下调对角质形成细胞的生物学命运具有直接意义，1-EBIO和相关化合物可能成为影响具有IK通道的各种非兴奋性细胞增殖的有效工具。
We used a combination of electrophysiological and cell and molecular biological techniques to study the regulation and functional role of the intermediate conductance Ca2+-activated K+ channel, hIK1, in HaCaT keratinocytes. When we incubated cells with the hIK1 opener, 1-ethyl-2-benzimidazolinone (1-EBIO), to investigate the cellular consequences of prolonged channel activity, an unexpected down-regulation of channels occurred within a few hours. The same effect was produced by the hIK1 openers chlorzoxazone and zoxazolamine and was also observed in a different cell line (C6 glioma cells). After 3 days of treatment with 1-EBIO, mRNA levels of hIK1 were substantially diminished and no channel activity was detected. Down-regulation of hIK1 was accompanied by a loss of mitogenic activity and a strong increase in cell size. After withdrawal of 1-EBIO, hIK1 mRNA and channel activity fully recovered and the cells resumed mitogenic activity. Our data present evidence for a novel feedback mechanism of hIK1 expression that appears to result from the paradoxical action of its pharmacological activator during prolonged application. Because the down-regulation of hIK1 bears immediate significance on the biological fate of keratinocytes, 1-EBIO and related compounds might emerge as potent tools to influence the proliferation of various non-excitable cells endowed with IK channels.
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DOI：
10.1073/pnas.97.14.8151
发表时间：
2000-07-05
影响因子：
11.1
作者：
Wulff, H;Miller, MJ;Chandy, KG
通讯作者：
Chandy, KG
角质形成细胞 K 通道介导 Ca2 诱导的分化。
DOI：
10.1111/1523-1747.ep12292585
发表时间：
1997
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Mauro,T;Dixon,DB;Komuves,L;Hanley,K;Pappone,PA
通讯作者：
Pappone,PA
影响因子：
15.9
作者：
PILLAI, S;BIKLE, DD
通讯作者：
BIKLE, DD
艾利希腹水肿瘤细胞的调节体积减少不是由细胞内钙的增加介导的。
DOI：
10.1016/0005-2736(93)90341-v
发表时间：
1993
期刊：
Biochimica et biophysica acta
影响因子：
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作者：
Young,RJ;Smith,TC;Levinson,C
通讯作者：
Levinson,C
氯唑沙宗刺激 Cl(-) 分泌。
DOI：
--
发表时间：
2000
期刊：
The Journal of pharmacology and experimental therapeutics.
影响因子：
--
作者：
Singh,AK;Devor,DC;Gerlach,AC;Gondor,M;Pilewski,JM;Bridges,RJ
通讯作者：
Bridges,RJ