Using the nematode C. elegans, researchers in Jonathan Pierce-Shimomura’s lab at the University of Texas, Austin previously showed that the BK potassium channel mediates alcohol intoxication in many species, from invertebrates to humans. Seeking to apply this information to develop treatments for individuals with alcohol disorders, he and his colleagues began looking for a way to make the worm resistant to intoxication.
Worms with the mutant channel showed their resistance to intoxication by reducing their egg-laying by only 6.3% when exposed to alcohol, compared to an 80.7% reduction in wild type worms. While reduced egg-laying may not seem particularly relevant to humans, the drunk worms also exhibited a reduced rate of locomotion, like an inebriated person having trouble leaving a bar. By contrast, the mutant worms crawled farther away from a starting point than their wild-type colleagues.
Transgenic worms with wild-type or mutant BK channels showed similar results. In mutant worms, the BK channel’s other normal functions, such as acting as a brake for neural and muscular activity, remained intact. “This is really important,” said Pierce-Shimomura. “If alcohol researchers are going to target a particular protein someday for treatment of alcohol disorders, it’s a dangerous protein to target, because if you turn it off, you may give people seizures. This research suggests that you could potentially prevent alcohol from activating it without compromising its normal function.”
Pierce-Shimomura envisions several applications of his research for humans and hopes to apply this information one day to help alcoholics get through withdrawal or to make alcohol less appealing. But whether worms will benefit from having at least one sober companion to guide them when everyone else is drunk remains to be seen.
Davis SJ, Scott LL, Hu K, Pierce-Shimomura JT. 2014. Conserved Single Residue in the BK Potassium Channel Required for Activation by Alcohol and Intoxication in C. elegans. J Neurosci 34(29):9562-9573.