Abstract
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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence / genetics
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Animals
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Base Sequence / genetics
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Behavior, Animal / drug effects
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Behavior, Animal / physiology
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Caenorhabditis elegans / drug effects*
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Caenorhabditis elegans / metabolism
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Caenorhabditis elegans Proteins
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Drug Resistance / drug effects
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Drug Resistance / genetics
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Ethanol / pharmacology*
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Large-Conductance Calcium-Activated Potassium Channels
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Membrane Potentials / drug effects
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Membrane Potentials / genetics
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Molecular Sequence Data
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Motor Activity / drug effects
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Motor Activity / genetics
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Mutation / drug effects
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Mutation / genetics
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Neural Inhibition / drug effects
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Neural Inhibition / genetics
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Neurons / drug effects*
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Neurons / metabolism
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Potassium Channels, Calcium-Activated / deficiency*
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Potassium Channels, Calcium-Activated / drug effects*
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Potassium Channels, Calcium-Activated / genetics
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Synaptic Transmission / drug effects
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Synaptic Transmission / genetics
Substances
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Caenorhabditis elegans Proteins
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Large-Conductance Calcium-Activated Potassium Channels
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Potassium Channels, Calcium-Activated
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slo-1 protein, C elegans
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Ethanol