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The Journal of Neuroscience, March 8, 2006, 26(10):2599-2613; doi:10.1523/JNEUROSCI.4314-05.2006
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Cellular/Molecular
A Common Ankyrin-G-Based Mechanism Retains KCNQ and NaV Channels at Electrically Active Domains of the Axon
Zongming Pan,1 Tingching Kao,1 Zsolt Horvath,1 Julia Lemos,1 Jai-Yoon Sul,2 Stephen D. Cranstoun,3 Vann Bennett,6 Steven S. Scherer,1,4 andEdward C. Cooper1,4,5 Departments of 1Neurology, 2Neuroscience, and 3Bioengineering and Institutes of 4Neurological Sciences and 5Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, and 6Department of Cell Biology and Howard Hughes Medical Institute, Duke University, Durham, North Carolina 27710
Correspondence should be addressed to Dr. Edward C. Cooper, Department of Neurology, University of Pennsylvania, 409 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104-6060. Email: edc{at}mail.med.upenn.edu
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
subunits that serves these functions. All identified NaV and KCNQ genes of worms, insects, and molluscs lack the ankyrin-G binding motif. In contrast, vertebrate orthologs of NaV
Key words: action potential; axon initial segment; node of Ranvier; neuromodulation; epilepsy; M-current
Received Oct. 10, 2005; revised Jan. 13, 2006; accepted Jan. 23, 2006.
Correspondence should be addressed to Dr. Edward C. Cooper, Department of Neurology, University of Pennsylvania, 409 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104-6060. Email: edc{at}mail.med.upenn.edu
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