Summary: Ethanol Tolerance Caused by slowpoke Induction
Roshani B. Cowmeadow, Harish R. Krishnan, Alfredo Ghezzi, Yazan M. Al'Hasan,
Yan Z. Wang, and Nigel S. Atkinson
Background: The large-conductance calcium-activated potassium channel encoded by the slow-
poke 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, induc-
tion 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