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 (49) Citing Articles via Google Scholar Google Scholar Articles by Lau, D. Articles by Rudy, B. Search for Related Content PubMed PubMed Citation Articles by Lau, D. Articles by Rudy, B.

 Previous Article  |  Next Article 

The Journal of Neuroscience, December 15, 2000, 20(24):9071-9085

Impaired Fast-Spiking, Suppressed Cortical Inhibition, and Increased Susceptibility to Seizures in Mice Lacking Kv3.2 K⁺ Channel Proteins

David Lau¹, Eleazar Vega-Saenz de Miera¹, Diego Contreras², Ander Ozaita¹, Michael Harvey¹, Alan Chow¹, Jeffrey L. Noebels³, Richard Paylor⁴, James I. Morgan⁵, Christopher S. Leonard⁶, and Bernardo Rudy¹

¹ Departments of Physiology and Neuroscience, and Biochemistry, New York University School of Medicine, New York, New York 10016, ² Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19106, Departments of ³ Neurology and ⁴ Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, ⁵ Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, and ⁶ Department of Physiology, New York Medical College, Valhalla, New York 10595

Voltage-gated K⁺ channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to 10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. We therefore generated mouse lines in which one of the Kv3 genes, Kv3.2, was disrupted by gene-targeting methods. Whole-cell electrophysiological recording showed that the ability to fire spikes at high frequencies was impaired in immunocytochemically identified FS interneurons of deep cortical layers (5-6) in which Kv3.2 proteins are normally prominent. No such impairment was found for FS neurons of superficial layers (2-4) in which Kv3.2 proteins are normally only weakly expressed. These data directly support the hypothesis that Kv3 channels are necessary for high-frequency firing. Moreover, we found that Kv3.2 / mice showed specific alterations in their cortical EEG patterns and an increased susceptibility to epileptic seizures consistent with an impairment of cortical inhibitory mechanisms. This implies that, rather than producing hyperexcitability of the inhibitory interneurons, Kv3.2 channel elimination suppresses their activity. These data suggest that normal cortical operations depend on the ability of inhibitory interneurons to generate high-frequency firing.

Key words: K⁺ channels; neocortex; fast spiking; knock-out inhibitory interneurons; high-frequency firing; seizure susceptibility; GABA; epilepsy

---

Copyright © 2000 Society for Neuroscience  0270-6474/00/20249071-15$05.00/0

This article has been cited by other articles:

				F. Espinosa, M. A. Torres-Vega, G. A. Marks, and R. H. Joho Ablation of Kv3.1 and Kv3.3 Potassium Channels Disrupts Thalamocortical Oscillations In Vitro and In Vivo J. Neurosci., May 21, 2008; 28(21): 5570 - 5581. [Abstract] [Full Text] [PDF]

				E. Zagha, E. J. Lang, and B. Rudy Kv3.3 Channels at the Purkinje Cell Soma Are Necessary for Generation of the Classical Complex Spike Waveform J. Neurosci., February 6, 2008; 28(6): 1291 - 1300. [Abstract] [Full Text] [PDF]

				M. Xu, R. Cao, R. Xiao, M. X. Zhu, and C. Gu The Axon Dendrite Targeting of Kv3 (Shaw) Channels Is Determined by a Targeting Motif That Associates with the T1 Domain and Ankyrin G J. Neurosci., December 19, 2007; 27(51): 14158 - 14170. [Abstract] [Full Text] [PDF]

				M. R. Kasten, B. Rudy, and M. P. Anderson Differential regulation of action potential firing in adult murine thalamocortical neurons by Kv3.2, Kv1, and SK potassium and N-type calcium channels J. Physiol., October 15, 2007; 584(2): 565 - 582. [Abstract] [Full Text] [PDF]

				I. Ogiwara, H. Miyamoto, N. Morita, N. Atapour, E. Mazaki, I. Inoue, T. Takeuchi, S. Itohara, Y. Yanagawa, K. Obata, et al. Nav1.1 Localizes to Axons of Parvalbumin-Positive Inhibitory Interneurons: A Circuit Basis for Epileptic Seizures in Mice Carrying an Scn1a Gene Mutation J. Neurosci., May 30, 2007; 27(22): 5903 - 5914. [Abstract] [Full Text] [PDF]

				C. Itami, F. Kimura, and S. Nakamura Brain-Derived Neurotrophic Factor Regulates the Maturation of Layer 4 Fast-Spiking Cells after the Second Postnatal Week in the Developing Barrel Cortex J. Neurosci., February 28, 2007; 27(9): 2241 - 2252. [Abstract] [Full Text] [PDF]

				I-F. Peng and C.-F. Wu Differential Contributions of Shaker and Shab K+ Currents to Neuronal Firing Patterns in Drosophila J Neurophysiol, January 1, 2007; 97(1): 780 - 794. [Abstract] [Full Text] [PDF]

				F. Lang, C. Bohmer, M. Palmada, G. Seebohm, N. Strutz-Seebohm, and V. Vallon (Patho)physiological Significance of the Serum- and Glucocorticoid-Inducible Kinase Isoforms. Physiol Rev, October 1, 2006; 86(4): 1151 - 1178. [Abstract] [Full Text] [PDF]

				E. M. Goldberg, S. Watanabe, S. Y. Chang, R. H. Joho, Z. J. Huang, C. S. Leonard, and B. Rudy Specific Functions of Synaptically Localized Potassium Channels in Synaptic Transmission at the Neocortical GABAergic Fast-Spiking Cell Synapse J. Neurosci., May 25, 2005; 25(21): 5230 - 5235. [Abstract] [Full Text] [PDF]

				L. Yan, J. Herrington, E. Goldberg, P. M. Dulski, R. M. Bugianesi, R. S. Slaughter, P. Banerjee, R. M. Brochu, B. T. Priest, G. J. Kaczorowski, et al. Stichodactyla helianthus Peptide, a Pharmacological Tool for Studying Kv3.2 Channels Mol. Pharmacol., May 1, 2005; 67(5): 1513 - 1521. [Abstract] [Full Text] [PDF]

				F. R. Fernandez, W. H. Mehaffey, M. L. Molineux, and R. W. Turner High-Threshold K+ Current Increases Gain by Offsetting a Frequency-Dependent Increase in Low-Threshold K+ Current J. Neurosci., January 12, 2005; 25(2): 363 - 371. [Abstract] [Full Text] [PDF]

				J. R. Gibson, M. Beierlein, and B. W. Connors Functional Properties of Electrical Synapses Between Inhibitory Interneurons of Neocortical Layer 4 J Neurophysiol, January 1, 2005; 93(1): 467 - 480. [Abstract] [Full Text] [PDF]

				T. Gloveli, T. Dugladze, S. Saha, H. Monyer, U. Heinemann, R. D. Traub, M. A. Whittington, and t. l. E. H. Buhl Differential involvement of oriens/pyramidale interneurones in hippocampal network oscillations in vitro J. Physiol., January 1, 2005; 562(1): 131 - 147. [Abstract] [Full Text] [PDF]

				A. Ozaita, J. Petit-Jacques, B. Volgyi, C. S. Ho, R. H. Joho, S. A. Bloomfield, and B. Rudy A Unique Role for Kv3 Voltage-Gated Potassium Channels in Starburst Amacrine Cell Signaling in Mouse Retina J. Neurosci., August 18, 2004; 24(33): 7335 - 7343. [Abstract] [Full Text] [PDF]

				M. T. Perez-Garcia, O. Colinas, E. Miguel-Velado, A. Moreno-Dominguez, and J. R. Lopez-Lopez Characterization of the Kv channels of mouse carotid body chemoreceptor cells and their role in oxygen sensing J. Physiol., June 1, 2004; 557(2): 457 - 471. [Abstract] [Full Text] [PDF]

				A. Lewis, Z. A. McCrossan, and G. W. Abbott MinK, MiRP1, and MiRP2 Diversify Kv3.1 and Kv3.2 Potassium Channel Gating J. Biol. Chem., February 27, 2004; 279(9): 7884 - 7892. [Abstract] [Full Text] [PDF]

				Z. A. McCrossan, A. Lewis, G. Panaghie, P. N. Jordan, D. J. Christini, D. J. Lerner, and G. W. Abbott MinK-Related Peptide 2 Modulates Kv2.1 and Kv3.1 Potassium Channels in Mammalian Brain J. Neurosci., September 3, 2003; 23(22): 8077 - 8091. [Abstract] [Full Text] [PDF]

				C.-C. Lien and P. Jonas Kv3 Potassium Conductance is Necessary and Kinetically Optimized for High-Frequency Action Potential Generation in Hippocampal Interneurons J. Neurosci., March 15, 2003; 23(6): 2058 - 2068. [Abstract] [Full Text] [PDF]

				D. M. Porcello, C. S. Ho, R. H. Joho, and J. R. Huguenard Resilient RTN Fast Spiking in Kv3.1 Null Mice Suggests Redundancy in the Action Potential Repolarization Mechanism J Neurophysiol, March 1, 2002; 87(3): 1303 - 1310. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help