title: KCNQ-SMIT complex formation facilitates ion channel-solute transporter cross talk.
abstract: Voltage-gated potassium channels formed by KCNQ2 and KCNQ3 are essential for normal neuronal excitability. KCNQ2/3 channel activity is augmentedin vivoby phosphatidylinositol 4,5-bisphosphate (PIP2), which is generated frommyo-inositol, an osmolyte transported into cells by sodium-dependentmyo-inositol transporters (SMITs). Here, we discovered that KCNQ2/3 channels isoform-specifically colocalize with SMIT1 and SMIT2 at sciatic nerve nodes of Ranvier and in axon initial segments, and form channel-transporter complexesin vitroandin vivoKCNQ2/3 coexpression protected SMIT1 activity from the otherwise inhibitory effects of cellular depolarization imposed by elevating extracellular [K+], and KCNQ2 was required for potentiation of SMIT activity bymyo-inositol preincubation. Cytoskeletal disruption, which speeds PIP2dispersion, attenuated potentiation of KCNQ2/3 currents by SMIT1-mediatedmyo-inositol uptake, suggesting close channel-transporter juxtaposition ensures KCNQ2/3 exposure to locally highmyo-inositol-derived PIP2concentrations. Thus, KCNQ2/3-SMIT1/2 coassembly permits cross talkviaphysical interaction, and may also be required for optimal, reciprocal indirect regulationviamembrane potential and PIP2, especially within the specialized architecture of axons.-Neverisky, D. L., Abbott, G. W. KCNQ-SMIT complex formation facilitates ion channel-solute transporter cross talk.
authors.affiliation: Bioelectricity Laboratory, Department of Pharmacology, and Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, California, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Neverisky
authors.affiliation: Bioelectricity Laboratory, Department of Pharmacology, and Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, California, USA abbottg@uci.edu.
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Abbott
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D051656:KCNQ Potassium Channels / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009865:Oocytes / Q000378:metabolism; D020033:Protein Isoforms; D021381:Protein Transport; D051381:Rats; D012584:Sciatic Nerve / Q000378:metabolism; D015398:Signal Transduction; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D051656:KCNQ Potassium Channels; D020033:Protein Isoforms; D027981:Symporters; C571821:sodium-myo-inositol cotransporter, rat
keywords: PIP2; SMIT1; SMIT2; myo-inositol; sciatic nerve