QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science 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 ISI Web of Science (24) Citing Articles via Google Scholar Google Scholar Articles by Zhou, L. Articles by Chiu, S. Y. Search for Related Content PubMed PubMed Citation Articles by Zhou, L. Articles by Chiu, S. Y. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB POTASSIUM

 Previous Article  |  Next Article 

The Journal of Neuroscience, July 15, 1999, 19(14):5768-5781

Determinants of Excitability at Transition Zones in Kv1.1-Deficient Myelinated Nerves

Lei Zhou¹, Albee Messing², and Shing Yan Chiu¹

¹ Department of Physiology, University of Wisconsin School of Medicine, Madison, Wisconsin 53706, and ² Department of Pathobiological Sciences, School of Veterinary Medicine and Waisman Center, University of Wisconsin, Madison, Wisconsin 53706

This study examines the role of K channel segregation and fiber geometry at transition zones of mammalian nerve terminals in the peripheral nervous system. Mutant mice that are deficient in Kv1.1, a fast Shaker K channel normally localized beneath the myelin sheath, display three types of cooling-induced abnormal hyperexcitability localized to regions before the transition zones of myelinated nerves. The first type is stimulus-evoked nerve backfiring that is absent at birth, peaks at postnatal day 17 (P17), and subsides in adults. The second type is spontaneous activity that has a more delayed onset, peaks at P30, and also disappears in older mice (>P60). TEA greatly amplifies this spontaneous activity with an effective dosage of ~0.7 mM, and can induce its reappearance in older mutant mice (>P100). These first two types of hyperexcitability occur only in homozygous mutants that are completely devoid of Kv1.1. The third type occurs in heterozygotes and represents a synergism between a TEA-sensitive channel and Kv1.1. Heterozygotes exposed to TEA display no overt phenotype until a single stimulation is given, which is then followed by an indefinite phase of repetitive discharge. Computer modeling suggests that the excitability of the transition zone near the nerve terminal has at least two major determinants: the preterminal internodal shortening and axonal slow K channels. We suggest that variations in fiber geometry create sites of inherent instability that is normally stabilized by a synergism between myelin-concealed Kv1.1 and a slow, TEA-sensitive K channel.

Key words: potassium channel gene; homologous recombination; myelinated nerves; transition zones; nerve conduction; mouse

---

Copyright © 1999 Society for Neuroscience  0270-6474/99/19145768-14$05.00/0

This article has been cited by other articles:

				Z. Pan, T. Kao, Z. Horvath, J. Lemos, J.-Y. Sul, S. D. Cranstoun, V. Bennett, S. S. Scherer, and E. C. Cooper A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon. J. Neurosci., March 8, 2006; 26(10): 2599 - 2613. [Abstract] [Full Text] [PDF]

				J. J. Devaux, K. A. Kleopa, E. C. Cooper, and S. S. Scherer KCNQ2 Is a Nodal K+ Channel J. Neurosci., February 4, 2004; 24(5): 1236 - 1244. [Abstract] [Full Text] [PDF]

				S. Poliak, D. Salomon, H. Elhanany, H. Sabanay, B. Kiernan, L. Pevny, C. L. Stewart, X. Xu, S.-Y. Chiu, P. Shrager, et al. Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1 J. Cell Biol., September 15, 2003; 162(6): 1149 - 1160. [Abstract] [Full Text] [PDF]

				J. Devaux, G. Alcaraz, J. Grinspan, V. Bennett, R. Joho, M. Crest, and S. S. Scherer Kv3.1b Is a Novel Component of CNS Nodes J. Neurosci., June 1, 2003; 23(11): 4509 - 4518. [Abstract] [Full Text] [PDF]

				K. McCormack, J. X. Connor, L. Zhou, L. L. Ho, B. Ganetzky, S.-Y. Chiu, and A. Messing Genetic Analysis of the Mammalian K+ Channel beta Subunit Kvbeta 2 (Kcnab2) J. Biol. Chem., April 5, 2002; 277(15): 13219 - 13228. [Abstract] [Full Text] [PDF]

				C. C. McIntyre, A. G. Richardson, and W. M. Grill Modeling the Excitability of Mammalian Nerve Fibers: Influence of Afterpotentials on the Recovery Cycle J Neurophysiol, February 1, 2002; 87(2): 995 - 1006. [Abstract] [Full Text] [PDF]

				R. Bal and D. Oertel Potassium Currents in Octopus Cells of the Mammalian Cochlear Nucleus J Neurophysiol, November 1, 2001; 86(5): 2299 - 2311. [Abstract] [Full Text] [PDF]

				L. Zhou and S. Y. Chiu Computer Model for Action Potential Propagation Through Branch Point in Myelinated Nerves J Neurophysiol, January 1, 2001; 85(1): 197 - 210. [Abstract] [Full Text] [PDF]

				A. Vincent, N. J. Lautermilch, and N. C. Spitzer Antisense Suppression of Potassium Channel Expression Demonstrates Its Role in Maturation of the Action Potential J. Neurosci., August 15, 2000; 20(16): 6087 - 6094. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help