Potassium channels act as chemosensors for solute transporters

Rian Manville, Geoffrey Abbott

    Research output: Contribution to journalArticlepeer-review


    Potassium channels form physical complexes with solute transporters in vivo, yet little is known about their range of possible signaling modalities and the underlying mechanisms. The KCNQ2/3 potassium channel, which generates neuronal M-current, is voltage-gated and its activity is also stimulated by binding of various small molecules. KCNQ2/3 forms reciprocally regulating complexes with sodium-coupled myo-inositol transporters (SMITs) in mammalian neurons. Here, we report that the neurotransmitter γ-aminobutyric acid (GABA) and other small molecules directly regulate myo-inositol transport in rat dorsal root ganglia, and by human SMIT1-KCNQ2/3 complexes in vitro, by inducing a distinct KCNQ2/3 pore conformation. Reciprocally, SMIT1 tunes KCNQ2/3 sensing of GABA and related metabolites. Ion permeation and mutagenesis studies suggest that SMIT1 and GABA similarly alter KCNQ2/3 pore conformation but via different KCNQ subunits and molecular mechanisms. KCNQ channels therefore act as chemosensors to enable co-assembled myo-inositol transporters to respond to diverse stimuli including neurotransmitters, metabolites and drugs.

    Original languageEnglish
    Article number90
    Pages (from-to)1-11
    Number of pages11
    JournalCommunications Biology
    Issue number1
    Publication statusPublished - 28 Feb 2020

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