biostudies-literaturePan ZNICHD NIH HHSNINDS NIH HHSNIGMS NIH HHS2599-613https://www.ebi.ac.uk/biostudies/studies/S-EPMC6675151biostudies-literatureUnknown26(10)KCNQ (KV7) potassium channels underlie subthreshold M-currents that stabilize the neuronal resting potential and prevent repetitive firing of action potentials. Here, antibodies against four different KCNQ2 and KCNQ3 polypeptide epitopes show these subunits concentrated at the axonal initial segment (AIS) and node of Ranvier. AIS concentration of KCNQ2 and KCNQ3, like that of voltage-gated sodium (NaV) channels, is abolished in ankyrin-G knock-out mice. A short motif, common to KCNQ2 and KCNQ3, mediates both in vivo ankyrin-G interaction and retention of the subunits at the AIS. This KCNQ2/KCNQ3 motif is nearly identical to the sequence on NaV alpha subunits that serves these functions. All identified NaV and KCNQ genes of worms, insects, and molluscs lack the ankyrin-G binding motif. In cThe Journal of neuroscience : the official journal of the Society for NeuroscienceA common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon.PMC6675151P30 HD26979P30 NS047321R01 NS043174R01 NS049119R01 NS49119R01 NS41811T32-GM07517Sul JYPan ZKao THorvath ZLemos JCooper ECBennett VScherer SSCranstoun SDfalseA common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon.KCNQ (KV7) potassium channels underlie subthreshold M-currents that stabilize the neuronal resting potential and prevent repetitive firing of action potentials. Here, antibodies against four different KCNQ2 and KCNQ3 polypeptide epitopes show these subunits concentrated at the axonal initial segment (AIS) and node of Ranvier. AIS concentration of KCNQ2 and KCNQ3, like that of voltage-gated sodium (NaV) channels, is abolished in ankyrin-G knock-out mice. A short motif, common to KCNQ2 and KCNQ3, mediates both in vivo ankyrin-G interaction and retention of the subunits at the AIS. This KCNQ2/KCNQ3 motif is nearly identical to the sequence on NaV alpha subunits that serves these functions. All identified NaV and KCNQ genes of worms, insects, and molluscs lack the ankyrin-G binding motif. In c2006-01-01T00:00:00Z2006 Mar2025-05-29T21:46:14.492Z2025-05-29T21:46:14.492ZS-EPMC66751511652503910.1523/jneurosci.4314-05.200610.1523/JNEUROSCI.4314-05.2006