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FASEB J January 1, 2017; 31 (7): 2828-2838.

KCNQ-SMIT complex formation facilitates ion channel-solute transporter cross talk.

Neverisky DL , Abbott GW .

Voltage-gated potassium channels formed by KCNQ2 and KCNQ3 are essential for normal neuronal excitability. KCNQ2/3 channel activity is augmented in vivo by phosphatidylinositol 4,5-bisphosphate (PIP2), which is generated from myo-inositol, an osmolyte transported into cells by sodium-dependent myo-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 complexes in vitro and in vivo KCNQ2/3 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 by myo-inositol preincubation. Cytoskeletal disruption, which speeds PIP2 dispersion, attenuated potentiation of KCNQ2/3 currents by SMIT1-mediated myo-inositol uptake, suggesting close channel-transporter juxtaposition ensures KCNQ2/3 exposure to locally high myo-inositol-derived PIP2 concentrations. Thus, KCNQ2/3-SMIT1/2 coassembly permits cross talk via physical interaction, and may also be required for optimal, reciprocal indirect regulation via membrane 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.

PubMed ID: 28283543
PMC ID: PMC5472404
Article link: FASEB J
Grant support: R01 GM115189 NIGMS NIH HHS

Genes referenced: kcnq2 kcnq3 slc5a3

External Resources:

Abbott, 2014, Pubmed, Xenbase [+]

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