A central role of the BK potassium channel in behavioral responses to ethanol in C. elegans.
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.
Davies
Andrew G
AG
Ernest Gallo Clinic and Research Center, Department of Neurology, Program in Neuroscience, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608, USA.
Pierce-Shimomura
Jonathan T
JT
Kim
Hongkyun
H
VanHoven
Miri K
MK
Thiele
Tod R
TR
Bonci
Antonello
A
Bargmann
Cornelia I
CI
McIntire
Steven L
SL
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics; D000431:Ethanol / Q000494:pharmacology*; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000172:deficiency* / Q000187:drug effects* / Q000235:genetics; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; C494845:slo-1 protein, C elegans; D000431:Ethanol