Ethanol tolerance caused by slowpoke induction in Drosophila.
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.
Cowmeadow
Roshani B
RB
Section of Neurobiology and The Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, 78712-0248, USA.
Krishnan
Harish R
HR
Ghezzi
Alfredo
A
Al'Hasan
Yazan M
YM
Wang
Yan Z
YZ
Atkinson
Nigel S
NS
D000818:Animals; D019905:Benzyl Alcohol; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D004361:Drug Tolerance / Q000235:genetics*; D000431:Ethanol; D015870:Gene Expression; D006358:Hot Temperature; D006993:Hypnotics and Sedatives; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D019076:Transgenes / Q000235:genetics
D029721:Drosophila Proteins; D006993:Hypnotics and Sedatives; D051036:Large-Conductance Calcium-Activated Potassium Channels; D012333:RNA, Messenger; C494844:slo protein, Drosophila; D000431:Ethanol; D019905:Benzyl Alcohol