Abstract
Addictive disorders markedly affect the emotional, physical and financial wellbeing of individuals, placing a substantial burden on the healthcare system. With their widespread presence in the brain, large-conductance calcium and voltage-activated potassium (BK) channels play a crucial role in various aspects of neuronal function. They contribute to behavioral tolerance and are closely linked to neuronal activity and modulation through intracellular calcium levels. As such, BK channels serve as key models for investigating the mechanisms of the effects of alcohol. Investigating their role in alcohol tolerance provides a broader understanding of their physiological and pharmacological importance. The present systematic review examined the literature on the role of BK channels in alcohol tolerance and comprehensively explored the topic. For this purpose, two databases, Web of Science and PubMed, were searched, and studies published from 2000 until June, 2024 were included. After applying specific inclusion and exclusion criteria, 35 studies underwent analysis to present a chronological overview of BK channels and their relevance in alcohol tolerance development. The studies were categorized into four main groups, according to research conducted on: i) Fruit flies; ii) nematodes; iii) rodents; and iv) cell lines. Understanding the mechanisms through which alcohol interacts with these channels may help to elucidate the cellular and molecular mechanisms underlying alcohol tolerance. There is a growing interest in developing drugs that can precisely modulate BK channel activity to treat alcohol dependence and tolerance. However, additional studies are required to fully explain the complex mechanisms through which BK channels influence alcohol-related behaviors and to interpret these findings into clinical applications.