Lidocaine promotes the trafficking and functional expression of Na v1.8 sodium channels in mammalian cells

Juan Zhao, Rahima Ziane, Aurélien Chatelier, Michael E. O'Leary, Mohamed Chahine

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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 Nav1.8 channels encode for the rapidly inactivating TTX-sensitive and slowly inactivating TTX-resistant Na currents, respectively. Although the Nav1.7 channel expresses well in cultured mammalian cell lines, attempts to express the Nav1.8 channel using similar approaches has been met with limited success. The inability to heterologously express Nav1.8 has hampered detailed characterization of the biophysical properties and pharmacology of these channels. In this study, we investigated the determinants of Nav1.8 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 Nav1.8 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 Nav1.8 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 Nav1.8 channels.

Original languageEnglish (US)
Pages (from-to)467-477
Number of pages11
JournalJournal of Neurophysiology
Volume98
Issue number1
DOIs
StatePublished - Jul 2007

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

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