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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 5, 2006, 26(27):7172-7180; doi:10.1523/JNEUROSCI.1101-06.2006

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 (23) Citing Articles via Google Scholar Google Scholar Articles by Van Wart, A. Articles by Matthews, G. Search for Related Content PubMed PubMed Citation Articles by Van Wart, A. Articles by Matthews, G.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Impaired Firing and Cell-Specific Compensation in Neurons Lacking Na_v1.6 Sodium Channels

Audra Van Wart and Gary Matthews

Graduate Program in Neuroscience, Department of Neurobiology and Behavior, State University of New York, Stony Brook, New York 11794-5230

Correspondence should be addressed to Gary Matthews, Department of Neurobiology and Behavior, Centers for Molecular Medicine, State University of New York, Stony Brook, NY 11794-5230. Email: gary.g.matthews{at}sunysb.edu

The ability of neurons to fire precise patterns of action potentials is critical for encoding inputs and efficiently driving target neurons. At the axon initial segment and nodes of Ranvier, where nerve impulses are generated and propagated, a high density of Na_v1.2 sodium channels is developmentally replaced by Na_v1.6 channels. In retinal ganglion cells (GCs), this isoform switch coincides with the developmental transition from single spikes to repetitive firing. Also, Na_v1.6 channels are required for repetitive spiking in cerebellar Purkinje neurons. These previous observations suggest that the developmental appearance of Na_v1.6 underlies the transition to repetitive spiking in GCs. To test this possibility, we recorded from GCs of med (Na_v1.6-null) and wild-type mice during postnatal development. By postnatal day 18, when the switch to Na_v1.6 at GC initial segments is normally complete, the maximal sustained and instantaneous firing rates were lower in med than in wild-type GCs, demonstrating that Na_v1.6 channels are necessary to attain physiologically relevant firing frequencies in GCs. However, the firing impairment was milder than that reported previously in med Purkinje neurons, which prompted us to look for differences in compensatory sodium channel expression. Both Na_v1.2 and Na_v1.1 channels accumulated at initial segments and nodes of med GCs, sites normally occupied by Na_v1.6. In med Purkinje cells, only Na_v1.1 channels were found at initial segments, whereas in other brain regions, only Na_v1.2 was detected at med initial segments and nodes. Thus, compensatory mechanisms in channel isoform distribution are cell specific, which likely results in different firing properties.

Key words: sodium channel; initial segment; retina; retinal ganglion cell; development; Na_v1.6

---

Received March 14, 2006; revised May 25, 2006; accepted May 31, 2006.

Correspondence should be addressed to Gary Matthews, Department of Neurobiology and Behavior, Centers for Molecular Medicine, State University of New York, Stony Brook, NY 11794-5230. Email: gary.g.matthews{at}sunysb.edu

This article has been cited by other articles:

				L. A. Papale, B. Beyer, J. M. Jones, L. M. Sharkey, S. Tufik, M. Epstein, V. A. Letts, M. H. Meisler, W. N. Frankel, and A. Escayg Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spike-wave discharges and absence epilepsy in mice Hum. Mol. Genet., May 1, 2009; 18(9): 1633 - 1641. [Abstract] [Full Text] [PDF]

				A. Lorincz and Z. Nusser Cell-Type-Dependent Molecular Composition of the Axon Initial Segment J. Neurosci., December 31, 2008; 28(53): 14329 - 14340. [Abstract] [Full Text] [PDF]

				M. Royeck, M.-T. Horstmann, S. Remy, M. Reitze, Y. Yaari, and H. Beck Role of Axonal NaV1.6 Sodium Channels in Action Potential Initiation of CA1 Pyramidal Neurons J Neurophysiol, October 1, 2008; 100(4): 2361 - 2380. [Abstract] [Full Text] [PDF]

				K. P. Carlin, J. Liu, and L. M. Jordan Postnatal Changes in the Inactivation Properties of Voltage-Gated Sodium Channels Contribute to the Mature Firing Pattern of Spinal Motoneurons J Neurophysiol, June 1, 2008; 99(6): 2864 - 2876. [Abstract] [Full Text] [PDF]

				A. H. Gittis and S. du Lac Similar Properties of Transient, Persistent, and Resurgent Na Currents in GABAergic and Non-GABAergic Vestibular Nucleus Neurons J Neurophysiol, May 1, 2008; 99(5): 2060 - 2065. [Abstract] [Full Text] [PDF]

				J. M. Nerbonne, B. R. Gerber, A. Norris, and A. Burkhalter Electrical remodelling maintains firing properties in cortical pyramidal neurons lacking KCND2-encoded A-type K+ currents J. Physiol., March 15, 2008; 586(6): 1565 - 1579. [Abstract] [Full Text] [PDF]

				J. N. Mercer, C. S. Chan, T. Tkatch, J. Held, and D. J. Surmeier Nav1.6 Sodium Channels Are Critical to Pacemaking and Fast Spiking in Globus Pallidus Neurons J. Neurosci., December 5, 2007; 27(49): 13552 - 13566. [Abstract] [Full Text] [PDF]

				M. S. Martin, B. Tang, L. A. Papale, F. H. Yu, W. A. Catterall, and A. Escayg The voltage-gated sodium channel Scn8a is a genetic modifier of severe myoclonic epilepsy of infancy Hum. Mol. Genet., December 1, 2007; 16(23): 2892 - 2899. [Abstract] [Full Text] [PDF]

				D. C. Rotaru, D. A. Lewis, and G. Gonzalez-Burgos Dopamine D1 receptor activation regulates sodium channel-dependent EPSP amplification in rat prefrontal cortex pyramidal neurons J. Physiol., June 15, 2007; 581(3): 981 - 1000. [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]

				D. J. Margolis and P. B. Detwiler Different Mechanisms Generate Maintained Activity in ON and OFF Retinal Ganglion Cells J. Neurosci., May 30, 2007; 27(22): 5994 - 6005. [Abstract] [Full Text] [PDF]

				T. Boiko, M. Vakulenko, H. Ewers, C. C. Yap, C. Norden, and B. Winckler Ankyrin-Dependent and -Independent Mechanisms Orchestrate Axonal Compartmentalization of L1 Family Members Neurofascin and L1/Neuron-Glia Cell Adhesion Molecule J. Neurosci., January 17, 2007; 27(3): 590 - 603. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help