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A central role of the BK potassium channel in behavioral responses to ethanol in C. elegans.

Cell | Dec 12, 2003

The activities of many neuronal proteins are modulated by ethanol, but the fundamental mechanisms underlying behavioral effects of ethanol remain unclear. To identify mechanisms responsible for intoxication, we screened for Caenorhabditis elegans mutants with altered behavioral responses to ethanol. We found that slo-1 mutants, which were previously recognized as having slightly uncoordinated movement, are highly resistant to ethanol in two behavioral assays. Numerous loss-of-function slo-1 alleles emerged from our screens, indicating that slo-1 has a central role in ethanol responses. slo-1 encodes the BK potassium channel. Electrophysiological analysis shows that ethanol activates the channel in vivo, which would inhibit neuronal activity. Moreover, behaviors of slo-1 gain-of-function mutants resemble those of ethanol-intoxicated animals. These results demonstrate that selective activation of BK channels is responsible for acute intoxicating effects of ethanol in C. elegans. BK channel activation may explain a variety of behavioral responses to ethanol in invertebrate and vertebrate systems.

Pubmed ID: 14675531 RIS Download

Mesh terms: Amino Acid Sequence | Animals | Base Sequence | Behavior, Animal | Caenorhabditis elegans | Caenorhabditis elegans Proteins | Drug Resistance | Ethanol | Large-Conductance Calcium-Activated Potassium Channels | Membrane Potentials | Molecular Sequence Data | Motor Activity | Mutation | Neural Inhibition | Neurons | Potassium Channels, Calcium-Activated | Synaptic Transmission