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: 98/1/467    most recent 00117.2007v1 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 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 (1) Citing Articles via Google Scholar Google Scholar Articles by Zhao, J. Articles by Chahine, M. Search for Related Content PubMed PubMed Citation Articles by Zhao, J. Articles by Chahine, M.

Lidocaine Promotes the Trafficking and Functional Expression of Na_v1.8 Sodium Channels in Mammalian Cells

¹Le Centre de Recherche Université Laval Robert-Giffard and Department of Medicine, Laval University, Quebec, Quebec, Canada; and ²Jefferson Medical College, Jefferson University, Philadelphia, Pennsylvania

Submitted 2 February 2007; accepted in final form 9 May 2007

Nociceptive neurons of the dorsal root ganglion (DRG) express a combination of rapidly gating TTX-sensitive and slowly gating TTX-resistant Na currents, and the channels that produce these currents have been cloned. The Na_v1.7 and Na_v1.8 channels encode for the rapidly inactivating TTX-sensitive and slowly inactivating TTX-resistant Na currents, respectively. Although the Na_v1.7 channel expresses well in cultured mammalian cell lines, attempts to express the Na_v1.8 channel using similar approaches has been met with limited success. The inability to heterologously express Na_v1.8 has hampered detailed characterization of the biophysical properties and pharmacology of these channels. In this study, we investigated the determinants of Na_v1.8 expression in tsA201 cells, a transformed variant of HEK293 cells, using a combination of biochemistry, immunochemistry, and electrophysiology. Our data indicate that the unusually low expression levels of Na_v1.8 in tsA201 cells results from a trafficking defect that traps the channel protein in the endoplasmic reticulum. Incubating the cultured cells with the local anesthetic lidocaine dramatically enhanced the cell surface expression of functional Na_v1.8 channels. The biophysical properties of the heterologously expressed Na_v1.8 channel are similar but not identical to those of the TTX-resistant Na current of native DRG neurons, recorded under similar conditions. Our data indicate that the lidocaine acts as a molecular chaperone that promotes efficient trafficking and increased cell surface expression of Na_v1.8 channels.

This article has been cited by other articles:

				L. M. Sharkey, X. Cheng, V. Drews, D. A. Buchner, J. M. Jones, M. J. Justice, S. G. Waxman, S. D. Dib-Hajj, and M. H. Meisler The ataxia3 Mutation in the N-Terminal Cytoplasmic Domain of Sodium Channel Nav1.6 Disrupts Intracellular Trafficking J. Neurosci., March 4, 2009; 29(9): 2733 - 2741. [Abstract] [Full Text] [PDF]

				C.-F. Wang, P. Gerner, B. Schmidt, Z. Z. Xu, C. Nau, S.-Y. Wang, R.-R. Ji, and G. K. Wang Use of Bulleyaconitine A as an Adjuvant for Prolonged Cutaneous Analgesia in the Rat Anesth. Analg., October 1, 2008; 107(4): 1397 - 1405. [Abstract] [Full Text] [PDF]

				G. G. Schofield, H. L. Puhl 3rd, and S. R. Ikeda Properties of Wild-Type and Fluorescent Protein-Tagged Mouse Tetrodotoxin-Resistant Sodium Channel (NaV1.8) Heterologously Expressed in Rat Sympathetic Neurons J Neurophysiol, April 1, 2008; 99(4): 1917 - 1927. [Abstract] [Full Text] [PDF]