QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 20 February 2007
doi: 10.1242/jcs.03396

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.03396v1 120/6/953    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rasmussen, H. B. Articles by Schmitt, N. Search for Related Content PubMed PubMed Citation Articles by Rasmussen, H. B. Articles by Schmitt, N. Social Bookmarking                         What's this?

Requirement of subunit co-assembly and ankyrin-G for M-channel localization at the axon initial segment

¹ Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark
² Department of Pharmacology, School of Medicine, University of California, Davis, CA 95616, USA
³ Department of Biomedical Sciences, Dental School, University of Maryland, Baltimore, MD 21201, USA

^* Author for correspondence (e-mail: hannebr{at}mfi.ku.dk)

Accepted 9 January 2007

The potassium channel subunits KCNQ2 and KCNQ3 are believed to underlie the M current of hippocampal neurons. The M-type potassium current plays a key role in the regulation of neuronal excitability; however, the subcellular location of the ion channels underlying this regulation has been controversial. We report here that KCNQ2 and KCNQ3 subunits are localized to the axon initial segment of pyramidal neurons of adult rat hippocampus and in cultured hippocampal neurons. We demonstrate that the localization of the KCNQ2/3 channel complex to the axon initial segment is favored by co-expression of the two channel subunits. Deletion of the ankyrin-G-binding motif in both the KCNQ2 and KCNQ3 C-terminals leads to the disappearance of the complex from the axon initial segment, albeit the channel complex remains functional and still reaches the plasma membrane. We further show that although heteromeric assembly of the channel complex favours localization to the axon initial segment, deletion of the ankyrin-G-binding motif in KCNQ2 alone does not alter the subcellular localization of KCNQ2/3 heteromers. By contrast, deletion of the ankyrin-G-binding motif in KCNQ3 significantly reduces AIS enrichment of the complex, implicating KCNQ3 as a major determinant of M channel localization to the AIS.

Key words: KCNQ, M current, Epilepsy, Axon initial segment, Ankyrin-G, Targeting

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. V. Tzingounis and R. A. Nicoll Contribution of KCNQ2 and KCNQ3 to the medium and slow afterhyperpolarization currents PNAS, December 16, 2008; 105(50): 19974 - 19979. [Abstract] [Full Text] [PDF]

				H. Vacher, D. P. Mohapatra, and J. S. Trimmer Localization and Targeting of Voltage-Dependent Ion Channels in Mammalian Central Neurons Physiol Rev, October 1, 2008; 88(4): 1407 - 1447. [Abstract] [Full Text] [PDF]

				M. M. Shah, M. Migliore, I. Valencia, E. C. Cooper, and D. A. Brown Functional significance of axonal Kv7 channels in hippocampal pyramidal neurons PNAS, June 3, 2008; 105(22): 7869 - 7874. [Abstract] [Full Text] [PDF]

				Y. Haitin and B. Attali The C-terminus of Kv7 channels: a multifunctional module J. Physiol., April 1, 2008; 586(7): 1803 - 1810. [Abstract] [Full Text] [PDF]

				V. Bennett and J. Healy Being there: cellular targeting of voltage-gated sodium channels in the heart J. Cell Biol., January 10, 2008; 180(1): 13 - 15. [Abstract] [Full Text] [PDF]

				J. S. Lowe, O. Palygin, N. Bhasin, T. J. Hund, P. A. Boyden, E. Shibata, M. E. Anderson, and P. J. Mohler Voltage-gated Nav channel targeting in the heart requires an ankyrin-G dependent cellular pathway J. Cell Biol., January 10, 2008; 180(1): 173 - 186. [Abstract] [Full Text] [PDF]