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KCNQ‐SMIT complex formation facilitates ion channel‐solute transporter cross talk
Author(s) -
Neverisky Daniel L.,
Abbott Geoffrey W.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201601334r
Subject(s) - chemistry , biophysics , ion channel , inositol , depolarization , potassium channel , sodium channel , transporter , inward rectifier potassium ion channel , microbiology and biotechnology , biochemistry , biology , sodium , receptor , organic chemistry , gene
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 (PIP 2 ), 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 PIP 2 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 PIP 2 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 PIP 2 , especially within the specialized architecture of axons.—Neverisky, D. L., Abbott, G. W. KCNQ‐SMIT complex formation facilitates ion channel‐solute transporter cross talk. FASEB J. 31, 2828–2838 (2017). www.fasebj.org