This material is based on work supported by the National Science Foundation under Grant 0114716 and F.M. Jones and H.L. Bruce Endowed Graduate Fellowship in Addiction Biology to YZW and AG.
Ethanol Tolerance Caused by slowpoke Induction in Drosophila
Article first published online: 12 APR 2006
Alcoholism: Clinical and Experimental Research
Volume 30, Issue 5, pages 745–753, May 2006
How to Cite
Cowmeadow, Roshani. B., Krishnan, Harish. R., Ghezzi, A., Al'Hasan, Y., Wang, Yan. Z. and Atkinson, N. (2006), Ethanol Tolerance Caused by slowpoke Induction in Drosophila. Alcoholism: Clinical and Experimental Research, 30: 745–753. doi: 10.1111/j.1530-0277.2006.00087.x
- Issue published online: 12 APR 2006
- Article first published online: 12 APR 2006
- Received for publication November 2, 2005; accepted January 18, 2006.
- BK Channel;
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.