The human gene KCNMA1 encodes a subunit of the primary BK ("big potassium") channel in human, a high-conductance calcium- and voltage-dependent potassium channel ("big" refers to the high conductance). BK channels are a known target of ethanol. There is a single orthologous gene in Drosophila, slo, for which classical loss-of-function and amorphic mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\slo is also orthologous to a second human gene, KCNU1.
A UAS construct of a tagged human Hsap\KCNMA1 gene has been introduced into flies, but has not been characterized in the context of this disease model.
Animals homozygous for amorphic alleles of Dmel\slo survive to adulthood; they exhibit multiple neurophysiology and behavioral defects, including circadian rhythm defects. In terms of response to alcohol, initial studies demonstrated that mutations in Dmel\slo affect development of tolerance; ethanol and benzyl alcohol were shown to be affected similarly and to produce mutual cross-tolerance. Dmel\slo mutations have been used to characterize the relationship between tolerance and withdrawal; withdrawal seizures are observed in this Drosophila system. (Note that human KCNMA1 is implicated in two diseases associated with seizures; see OMIM:609446 and OMIM:617643.) Physical and genetic interactions have been described for Dmel\slo; see below and in the slo gene report.
[updated Feb. 2019 by FlyBase; FBrf0222196]