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 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 Web of Science (58) Citing Articles via Google Scholar Google Scholar Articles by Malin, S. A. Articles by Nerbonne, J. M. Search for Related Content PubMed PubMed Citation Articles by Malin, S. A. Articles by Nerbonne, J. M.

 Previous Article  |  Next Article 

The Journal of Neuroscience, July 15, 2000, 20(14):5191-5199

Elimination of the Fast Transient in Superior Cervical Ganglion Neurons with Expression of KV4.2W362F: Molecular Dissection of I_A

Sacha A. Malin and Jeanne M. Nerbonne

Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110

Electrophysiological and molecular studies have revealed considerable heterogeneity in voltage-gated K⁺ currents and in the subunits that underlie these channels in mammalian neurons. At present, however, the relationship between native K⁺ currents and cloned subunits is poorly understood. In the experiments here, a molecular genetic approach was exploited to define the molecular correlate of the fast transient outward K⁺ current, I_Af, in sympathetic neurons and to explore the functional role of I_Af in shaping action potential waveforms and controlling repetitive firing patterns. Using the biolistic gene gun, cDNAs encoding a dominant negative mutant Kv4.2 -subunit (Kv4.2W362F) and enhanced green fluorescent protein (EGFP) were introduced into rat sympathetic neurons in vitro. Whole-cell voltage-clamp recordings obtained from EGFP-positive cells revealed that I_Af is selectively eliminated in cells expressing Kv4.2W362F, demonstrating that Kv4 -subunits underlie I_Af in sympathetic neurons. In addition, I_Af density is increased significantly in cells overexpressing wild-type Kv4.2. In cells expressing Kv4.2W362F, input resistances are increased and (current) thresholds for action potential generation are decreased, demonstrating that I_Af plays a pivotal role in regulating excitability. Expression of Kv4.2W362F and elimination of I_Af also alters the distribution of repetitive firing patterns observed in response to a prolonged injection of depolarizing current. The wild-type superior cervical ganglion is composed of phasic, adapting, and tonic firing neurons. Elimination of I_Af increases the percentage of adapting cells by shifting phasic cells to the adapting firing pattern, and increased I_Af density reduces the number of adapting cells.

Key words: K⁺ channels; I_A; Kv4 -subunits; Kv4.2W362F; transgenics; gene gun; neuronal excitability; repetitive firing patterns

---

Copyright © 2000 Society for Neuroscience  0270-6474/00/20145191-09$05.00/0

This article has been cited by other articles:

				E. Lorenzetto, L. Caselli, G. Feng, W. Yuan, J. M. Nerbonne, J. R. Sanes, and M. Buffelli Genetic perturbation of postsynaptic activity regulates synapse elimination in developing cerebellum PNAS, September 22, 2009; 106(38): 16475 - 16480. [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]

				Z. Jia, J. Bei, L. Rodat-Despoix, B. Liu, Q. Jia, P. Delmas, and H. Zhang NGF Inhibits M/KCNQ Currents and Selectively Alters Neuronal Excitability in Subsets of Sympathetic Neurons Depending on their M/KCNQ Current Background J. Gen. Physiol., June 1, 2008; 131(6): 575 - 587. [Abstract] [Full Text] [PDF]

				H. Soh and S. A. N. Goldstein ISA Channel Complexes Include Four Subunits Each of DPP6 and Kv4.2 J. Biol. Chem., May 30, 2008; 283(22): 15072 - 15077. [Abstract] [Full Text] [PDF]

				A. C. Jackson and B. P. Bean State-Dependent Enhancement of Subthreshold A-Type Potassium Current by 4-Aminopyridine in Tuberomammillary Nucleus Neurons J. Neurosci., October 3, 2007; 27(40): 10785 - 10796. [Abstract] [Full Text] [PDF]

				A. Ruiz-Gomez, B. Mellstrom, D. Tornero, E. Morato, M. Savignac, H. Holguin, K. Aurrekoetxea, P. Gonzalez, C. Gonzalez-Garcia, V. Cena, et al. G Protein-coupled Receptor Kinase 2-mediated Phosphorylation of Downstream Regulatory Element Antagonist Modulator Regulates Membrane Trafficking of Kv4.2 Potassium Channel J. Biol. Chem., January 12, 2007; 282(2): 1205 - 1215. [Abstract] [Full Text] [PDF]

				H. Misonou, M. Menegola, D. P. Mohapatra, L. K. Guy, K.-S. Park, and J. S. Trimmer Bidirectional Activity-Dependent Regulation of Neuronal Ion Channel Phosphorylation J. Neurosci., December 27, 2006; 26(52): 13505 - 13514. [Abstract] [Full Text] [PDF]

				A. Burkhalter, Y. Gonchar, R. L. Mellor, and J. M. Nerbonne Differential Expression of IA Channel Subunits Kv4.2 and Kv4.3 in Mouse Visual Cortical Neurons and Synapses. J. Neurosci., November 22, 2006; 26(47): 12274 - 12282. [Abstract] [Full Text] [PDF]

				X. Ma, K. Bielefeldt, Z. Y. Tan, C. A. Whiteis, V. Snitsarev, F. M. Abboud, and M. W. Chapleau Dual mechanisms of angiotensin-induced activation of mouse sympathetic neurones J. Physiol., May 15, 2006; 573(1): 45 - 63. [Abstract] [Full Text] [PDF]

				O. Sacchi, M. L. Rossi, R. Canella, and R. Fesce Synaptic and Somatic Effects of Axotomy in the Intact, Innervated Rat Sympathetic Neuron J Neurophysiol, May 1, 2006; 95(5): 2832 - 2844. [Abstract] [Full Text] [PDF]

				J. Kim, D.-S. Wei, and D. A. Hoffman Kv4 potassium channel subunits control action potential repolarization and frequency-dependent broadening in rat hippocampal CA1 pyramidal neurones J. Physiol., November 15, 2005; 569(1): 41 - 57. [Abstract] [Full Text] [PDF]

				H. H Jerng, K. Kunjilwar, and P. J Pfaffinger Multiprotein assembly of Kv4.2, KChIP3 and DPP10 produces ternary channel complexes with ISA-like properties J. Physiol., November 1, 2005; 568(3): 767 - 788. [Abstract] [Full Text] [PDF]

				W. Yuan, A. Burkhalter, and J. M. Nerbonne Functional Role of the Fast Transient Outward K+ Current IA in Pyramidal Neurons in (Rat) Primary Visual Cortex J. Neurosci., October 5, 2005; 25(40): 9185 - 9194. [Abstract] [Full Text] [PDF]

				D. L. B. Winkelman, C. L. Beck, D. L. Ypey, and M. E. O'Leary Inhibition of the A-Type K+ Channels of Dorsal Root Ganglion Neurons by the Long-Duration Anesthetic Butamben J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1177 - 1186. [Abstract] [Full Text] [PDF]

				F. Aimond, S. P. Kwak, K. J. Rhodes, and J. M. Nerbonne Accessory Kv{beta}1 Subunits Differentially Modulate the Functional Expression of Voltage-Gated K+ Channels in Mouse Ventricular Myocytes Circ. Res., March 4, 2005; 96(4): 451 - 458. [Abstract] [Full Text] [PDF]

				N. Gamper, V. Reznikov, Y. Yamada, J. Yang, and M. S. Shapiro Phosphotidylinositol 4,5-Bisphosphate Signals Underlie Receptor-Specific Gq/11-Mediated Modulation of N-Type Ca2+ Channels J. Neurosci., December 1, 2004; 24(48): 10980 - 10992. [Abstract] [Full Text] [PDF]

				A. P. Berg, E. M. Talley, J. P. Manger, and D. A. Bayliss Motoneurons Express Heteromeric TWIK-Related Acid-Sensitive K+ (TASK) Channels Containing TASK-1 (KCNK3) and TASK-3 (KCNK9) Subunits J. Neurosci., July 28, 2004; 24(30): 6693 - 6702. [Abstract] [Full Text] [PDF]

				R. Shibata, H. Misonou, C. R. Campomanes, A. E. Anderson, L. A. Schrader, L. C. Doliveira, K. I. Carroll, J. D. Sweatt, K. J. Rhodes, and J. S. Trimmer A Fundamental Role for KChIPs in Determining the Molecular Properties and Trafficking of Kv4.2 Potassium Channels J. Biol. Chem., September 19, 2003; 278(38): 36445 - 36454. [Abstract] [Full Text] [PDF]

				S. Hattori, F. Murakami, and W.-J. Song Quantitative Relationship Between Kv4.2 mRNA and A-Type K+ Current in Rat Striatal Cholinergic Interneurons During Development J Neurophysiol, July 1, 2003; 90(1): 175 - 183. [Abstract] [Full Text] [PDF]

				N. Gamper and M. S. Shapiro Calmodulin Mediates Ca2+-dependent Modulation of M-type K+ Channels J. Gen. Physiol., June 30, 2003; 122(1): 17 - 31. [Abstract] [Full Text] [PDF]

				S. A. Malin and J. M. Nerbonne Delayed Rectifier K+ Currents, IK, Are Encoded by Kv2 alpha -Subunits and Regulate Tonic Firing in Mammalian Sympathetic Neurons J. Neurosci., December 1, 2002; 22(23): 10094 - 10105. [Abstract] [Full Text] [PDF]

				J. Mitterdorfer and B. P. Bean Potassium Currents during the Action Potential of Hippocampal CA3 Neurons J. Neurosci., December 1, 2002; 22(23): 10106 - 10115. [Abstract] [Full Text] [PDF]

				T. Sacco and F. Tempia A-Type potassium currents active at subthreshold potentials in mouse cerebellar purkinje cells J. Physiol., September 1, 2002; 543(2): 505 - 520. [Abstract] [Full Text] [PDF]

				E. J Beck, M. Bowlby, W F. An, K. J Rhodes, and M. Covarrubias Remodelling inactivation gating of Kv4 channels by KChIP1, a small-molecular-weight calcium-binding protein J. Physiol., February 1, 2002; 538(3): 691 - 706. [Abstract] [Full Text] [PDF]

				V. Riazanski, A. Becker, J. Chen, D. Sochivko, A. Lie, O. D Wiestler, C. E Elger, and H. Beck Functional and molecular analysis of transient voltage-dependent K+ currents in rat hippocampal granule cells J. Physiol., December 1, 2001; 537(2): 391 - 406. [Abstract] [Full Text] [PDF]

				M. N. Rasband, E. W. Park, T. W. Vanderah, J. Lai, F. Porreca, and J. S. Trimmer Distinct potassium channels on pain-sensing neurons PNAS, November 6, 2001; 98(23): 13373 - 13378. [Abstract] [Full Text] [PDF]

				S. A. Malin and J. M. Nerbonne Molecular Heterogeneity of the Voltage-Gated Fast Transient Outward K+ Current, IAf, in Mammalian Neurons J. Neurosci., October 15, 2001; 21(20): 8004 - 8014. [Abstract] [Full Text] [PDF]

				L. Tatulian, P. Delmas, F. C. Abogadie, and D. A. Brown Activation of Expressed KCNQ Potassium Currents and Native Neuronal M-Type Potassium Currents by the Anti-Convulsant Drug Retigabine J. Neurosci., August 1, 2001; 21(15): 5535 - 5545. [Abstract] [Full Text] [PDF]

				A. A. Selyanko, P. Delmas, J. K. Hadley, L. Tatulian, I. C. Wood, M. Mistry, B. London, and D. A. Brown Dominant-Negative Subunits Reveal Potassium Channel Families That Contribute to M-Like Potassium Currents J. Neurosci., March 1, 2002; 22(5): RC212 - RC212. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help