The sodium channel Nav1.5a is the predominant isoform expressed in adult mouse dorsal root ganglia and exhibits distinct inactivation properties from the full-length Nav1.5 channel

Mol Cell Neurosci. 2007 Jun;35(2):283-91. doi: 10.1016/j.mcn.2007.03.002. Epub 2007 Mar 13.

Abstract

Nav1.5 is the principal voltage-gated sodium channel expressed in heart, and is also expressed at lower abundance in embryonic dorsal root ganglia (DRG) with little or no expression reported postnatally. We report here the expression of Nav1.5 mRNA isoforms in adult mouse and rat DRG. The major isoform of mouse DRG is Nav1.5a, which encodes a protein with an IDII/III cytoplasmic loop reduced by 53 amino acids. Western blot analysis of adult mouse DRG membrane proteins confirmed the expression of Nav1.5 protein. The Na+ current produced by the Nav1.5a isoform has a voltage-dependent inactivation significantly shifted to more negative potentials (by approximately 5 mV) compared to the full-length Nav1.5 when expressed in the DRG neuroblastoma cell line ND7/23. These results imply that the alternatively spliced exon 18 of Nav1.5 plays a role in channel inactivation and that Nav1.5a is likely to make a significant contribution to adult DRG neuronal function.

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Cell Line, Tumor
  • Ganglia, Spinal / metabolism*
  • Gene Expression / drug effects
  • Gene Expression / physiology*
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Mice
  • NAV1.5 Voltage-Gated Sodium Channel
  • Neuroblastoma
  • Patch-Clamp Techniques
  • Protein Isoforms / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sodium Channel Blockers / pharmacology
  • Sodium Channels / metabolism*
  • Tetrodotoxin / pharmacology
  • Transfection / methods

Substances

  • NAV1.5 Voltage-Gated Sodium Channel
  • Protein Isoforms
  • RNA, Messenger
  • Scn5a protein, mouse
  • Scn5a protein, rat
  • Sodium Channel Blockers
  • Sodium Channels
  • Tetrodotoxin