HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 97/2/1258    most recent 01033.2006v1 Alert me when this article is cited 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 (5) Citing Articles via Google Scholar Google Scholar Articles by Choi, J.-S. Articles by Waxman, S. G. Search for Related Content PubMed PubMed Citation Articles by Choi, J.-S. Articles by Waxman, S. G.

Differential Slow Inactivation and Use-Dependent Inhibition of Na_v1.8 Channels Contribute to Distinct Firing Properties in IB₄⁺ and IB₄^– DRG Neurons

¹Department of Neurology and ²Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven; and ³Rehabilitation Research Center, Veterans Administration Connecticut Healthcare System, West Haven, Connecticut

Submitted 27 September 2006; accepted in final form 10 November 2006

Nociceptive dorsal root ganglion (DRG) neurons can be classified into nonpeptidergic IB₄⁺ and peptidergic IB₄^– subtypes, which terminate in different layers in dorsal horn and transmit pain along different ascending pathways, and display different firing properties. Voltage-gated, tetrodotoxin-resistant (TTX-R) Na_v1.8 channels are expressed in both IB₄⁺ and IB₄^– cells and produce most of the current underlying the depolarizing phase of action potential (AP). Slow inactivation of TTX-R channels has been shown to regulate repetitive DRG neuron firing behavior. We show in this study that use-dependent reduction of Na_v1.8 current in IB₄⁺ neurons is significantly stronger than that in IB₄^– neurons, although voltage dependency of activation and steady-state inactivation are not different. The time constant for entry of Na_v1.8 into slow inactivation in IB₄⁺ neurons is significantly faster and more Na_v1.8 enter the slow inactivation state than in IB₄^– neurons. In addition, recovery from slow inactivation of Na_v1.8 in IB₄⁺ neurons is slower than that in IB₄^– neurons. Using current-clamp recording, we demonstrate a significantly higher current threshold for generation of APs and a longer latency to onset of firing in IB₄⁺, compared with those of IB₄^– neurons. In response to a ramp stimulus, IB₄⁺ neurons produce fewer APs and display stronger adaptation, with a faster decline of AP peak than IB₄^– neurons. Our data suggest that differential use-dependent reduction of Na_v1.8 current in these two DRG subpopulations, which results from their different rate of entry into and recovery from the slow inactivation state, contributes to functional differences between these two neuronal populations.

This article has been cited by other articles:

				A. Hudmon, J.-S. Choi, L. Tyrrell, J. A. Black, A. M. Rush, S. G. Waxman, and S. D. Dib-Hajj Phosphorylation of Sodium Channel Nav1.8 by p38 Mitogen-Activated Protein Kinase Increases Current Density in Dorsal Root Ganglion Neurons J. Neurosci., March 19, 2008; 28(12): 3190 - 3201. [Abstract] [Full Text] [PDF]

				A. M. Rush, T. R. Cummins, and S. G. Waxman Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons J. Physiol., February 15, 2007; 579(1): 1 - 14. [Abstract] [Full Text] [PDF]