A common ankyrin-G-based mechanism retains KCNQ and Na V channels at electrically active domains of the axon

Zongming Pan, Tingching Kao, Zsolt Horvath, Julia Lemos, Jai Yoon Sul, Stephen D. Cranstoun, Vann Bennett, Steven S. Scherer, Edward C. Cooper

Research output: Contribution to journalArticlepeer-review

367 Scopus citations

Abstract

KCNQ (K V7) 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 ofKCNQ2and KCNQ3, like that of voltage-gated sodium (Na V) 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 Na V α subunits that serves these functions. All identified Na V and KCNQ genes of worms, insects, and molluscs lack the ankyrin-G binding motif. In contrast, vertebrate orthologs of Na V α subunits, KCNQ2, and KCNQ3 (including from bony fish, birds, and mammals) all possess the motif. Thus, concerted ankyrin-G interaction with KCNQ and Na V channels appears to have arisen through convergent molecular evolution, after the division between invertebrate and vertebrate lineages, but before the appearance of the lastcommonjawed vertebrate ancestor. This includes the historical period when myelin also evolved.

Original languageEnglish (US)
Pages (from-to)2599-2613
Number of pages15
JournalJournal of Neuroscience
Volume26
Issue number10
DOIs
StatePublished - Mar 8 2006

Keywords

  • Action potential
  • Axon initial segment
  • Epilepsy
  • M-current
  • Neuromodulation
  • Node of Ranvier

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