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General Information
alcohol, response to, KCNMA1-related
FlyBase ID

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]

Disease Summary Information
Parent Disease Summary: alcohol use disorder, susceptibility to (fly models overview)
Symptoms and phenotype
Alcoholism can be defined as persistence of excessive drinking over a long period of time despite adverse health effects and disruption of social relations (Morozova et al., 2014; pubmed:24395673).
The 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM) combined the two former categorizations of abnormal alcohol use (alcohol abuse and alcohol dependence) into one diagnosis: alcohol use disorder. The severity of an individual's AUD is broken into classifications: mild, moderate, or severe. "Alcoholism" is a non-medical term often used to describe a severe form of alcohol use disorder. (
Excessive alcohol consumption is associated with increased risk of different types of cancer, higher cardiovascular disease mortality, birth defects, liver diseases, and neuropsychiatric disorders (Morozova et al., 2014; pubmed:24395673).
Alcoholism is a multifactorial, genetically influenced disorder. [from OMIM:103780; 2017.12.19]
Specific Disease Summary: alcohol, response to, KCNMA1-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Cellular phenotype and pathology
Molecular information
The large-conductance voltage- and Ca(2+)-activated K+ channel, also called the BK channel, differs from other K+ channels in that it can be activated by both intracellular Ca(2+) ions and by membrane depolarization. The BK channel consists of 4 alpha subunits and 4 optional auxiliary beta subunits. The pore-forming alpha subunit is encoded by the KCNMA1 gene, which produces multiple isoforms through alternative splicing. The 4 beta subunits are encoded by different genes that show tissue-specific expression (Sausbier et al., 2004; pubmed:15194823). [from OMIM:600150; 2017.12.20]
Mammalian BK channels are a known target of ethanol, with different effects and different mechanisms observed for acute vs. protracted exposure (reviewed in Dopico et al., 2014; pubmed:25538625).
Disease synonyms
alcohol, response to, BK-channel-related
AUD susceptibility, KCNMA1-related
AUD susceptibility, BK-channel-related
alcohol use disorder, susceptibility to (postulated), KCNMA1-related
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)
Many to one: 2 human to 1 Drosophila; the second human gene is KCNU1.
Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    slowpoke (slo) encodes the structural alpha subunit of a BK ('maxi K') calcium-activated potassium channel. It regulates neurotransmitter release at the synapse and maintain electrical excitability in neurons and muscle cells. [Date last reviewed: 2019-03-14]
    Gene Groups / Pathways
    Comments on ortholog(s)
    High-scoring ortholog of human KCNMA1; moderate-scoring ortholog of KCNU1 (1 Drosophila to 2 human). Dmel\slo shares 52% identity and 64% similarity with KCNMA1.
    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Synthetic Gene(s) Used (0)
    Summary of Physical Interactions (2 groups)
    Interacting group
    anti tag coimmunoprecipitation, western blot
    anti tag coimmunoprecipitation, western blot
    Alleles Reported to Model Human Disease (Disease Ontology) (0 alleles)
    Genetic Tools, Stocks and Reagents
    Sources of Stocks
    Contact lab of origin for a reagent not available from a public stock center.
    Bloomington Stock Center Disease Page
    Selected mammalian transgenes
    Publicly Available Stocks
    Selected Drosophila transgenes
    Publicly Available Stocks
    RNAi constructs available
    Publicly Available Stocks
    Selected Drosophila classical alleles
    Allele class
    Publicly Available Stocks
    loss of function allele
    gamma ray
    amorphic allele - molecular evidence
    References (21)