Cowmeadow Roshani B, Krishnan Harish R, Ghezzi Alfredo, Al'Hasan Yazan M, Wang Yan Z, Atkinson Nigel S
Section of Neurobiology and The Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, 78712-0248, USA.
Alcohol Clin Exp Res. 2006 May;30(5):745-53. doi: 10.1111/j.1530-0277.2006.00087.x.
The large-conductance calcium-activated potassium channel encoded by the slowpoke gene has recently been implicated in the ethanol response. Caenorhabditis elegans carrying mutations in this gene have altered ethanol sensitivity and Drosophila mutant for this gene are unable to acquire rapid tolerance to ethanol or anesthetics. In Drosophila, induction of slowpoke expression has been linked to anesthetic resistance.
We used Drosophila as a model system to examine the relationship between slowpoke expression and ethanol tolerance. Real-time PCR and a reporter transgene were used to measure slowpoke induction after ethanol sedation. An inducible slowpoke transgene was used to manipulate slowpoke levels in the absence of ethanol sedation.
Ethanol sedation increased transcription from the slowpoke neural promoters but not from the slowpoke muscle/tracheal cell promoters. This neural-specific change was concomitant with the appearance of ethanol tolerance, leading us to suspect linkage between the two. Moreover, induction of slowpoke expression from a transgene produced a phenotype that mimics ethanol tolerance.
In Drosophila, ethanol sedation induces slowpoke expression in the nervous system and results in ethanol tolerance. The induction of slowpoke expression alone is sufficient to produce a phenotype that is indistinguishable from true ethanol tolerance. Therefore, the regulation of the slowpoke BK-type channel gene must play an integral role in the Drosophila ethanol response.
由slowpoke基因编码的大电导钙激活钾通道最近被认为与乙醇反应有关。携带该基因突变的秀丽隐杆线虫乙醇敏感性发生改变，该基因的果蝇突变体无法快速获得对乙醇或麻醉剂的耐受性。在果蝇中，slowpoke表达的诱导与麻醉抗性有关。
我们以果蝇为模型系统来研究slowpoke表达与乙醇耐受性之间的关系。使用实时PCR和报告转基因来测量乙醇镇静后slowpoke的诱导情况。在无乙醇镇静的情况下，使用可诱导的slowpoke转基因来调控slowpoke水平。
乙醇镇静增加了slowpoke神经启动子的转录，但未增加slowpoke肌肉/气管细胞启动子的转录。这种神经特异性变化与乙醇耐受性的出现同时发生，使我们怀疑两者之间存在联系。此外，转基因诱导的slowpoke表达产生了一种模拟乙醇耐受性的表型。
在果蝇中，乙醇镇静诱导神经系统中slowpoke的表达并导致乙醇耐受性。单独诱导slowpoke表达就足以产生一种与真正的乙醇耐受性无法区分的表型。因此，slowpoke BK型通道基因的调控在果蝇乙醇反应中必定起着不可或缺的作用。
