Alcohol withdrawal is influenced by Slo channels
For people with alcohol dependence, withdrawal symptoms can cause relapse. Some physical symptoms—such as seizures, delirium tremens, and heart rhythm abnormalities—can be fatal, but even non-life-threatening symptoms like anxiety and confusion can trigger relapse.
The changes in the nervous system that underlie withdrawal symptoms may involve ion channels in the Slo family. The function of one such channel, Slo1, is modulated by alcohol in a variety of species, and mammalian tissues respond to chronic alcohol exposure by reducing the number of Slo1 channels and swapping them out for less alcohol-sensitive variants. In the July issue of GENETICS, Scott et al. report that in the nematode Caenorhabditis elegans, the behavioral effects of alcohol withdrawal are influenced by Slo1 function. Their work provides a glimpse into the molecular underpinnings of some of the neural changes that make recovery from alcohol use disorders so difficult.
As in humans, alcohol impairs behavior in C. elegans, as does alcohol withdrawal. The researchers mutationally disabled the C. elegans version of Slo1, paralleling the reduction in Slo1 function that results from prolonged alcohol exposure in mammalian cells. They found that the mutant worms were more resistant to intoxication but experienced far worse withdrawal periods. When they boosted ion channel function, the opposite happened to withdrawal behavior—it was less severe. Conversely, a second potassium channel, Slo2, appeared required for withdrawal behavior.
These results suggest that if Slo1 function could be enhanced or Slo2 function decreased in humans suffering from alcohol withdrawal, their symptoms could be dampened. Further research on the Slo family of ion channels may one day yield targets for drugs that lessen the effects of withdrawal, giving sufferers of alcohol use disorders a better chance of recovery.
Scott, L.; Davis, S.; Yen, R.; Ordemann, G.; Nordquist, S.; Bannai, D.; Pierce, J. Behavioral Deficits Following Withdrawal from Chronic Ethanol Are Influenced by SLO Channel Function in Caenorhabditis elegans.
GENETICS, 206(3), 1445-1458.