Dorsal root ganglia isolated from Nf1+/- mice exhibit increased levels of mRNA expression of voltage-dependent sodium channels

K. E. Hodgdon, C. M. Hingtgen, G. D. Nicol

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

We reported previously that sensory neurons isolated from mice with a heterozygous mutation of the Nf1 gene (Nf1+/-) exhibited greater excitability and increased sodium current densities compared with wildtype mice. This raises the question as to whether the increased current density resulted from post-translational modifications or increased expression of sodium channels. Quantitative real-time polymerase chain reaction was used to measure expression levels of the nine different voltage-gated sodium channel α subunits and the four associated auxiliary β subunits in the dorsal root ganglia (DRG) obtained from wildtype and Nf1+/- mice. The Relative Expression Software Tool indicated that Nav1.1, Nav1.3, Nav1.7, and Nav1.8 were significantly elevated in DRG isolated from Nf1+/- mice. Expression of Nav1.2, Nav1.5, Nav1.6, and Nav1.9 were not significantly altered. The gene transcript for Nav1.4 was not detected. There were no significant changes in the relative expression levels of β subunits. The Nav1.9 subtype was the most abundant with Nav1.7 and Nav1.8 being the next most abundant subtypes, whereas Nav1.3 was relatively less abundant. For the β subunits, β1 was by far the most abundant subtype. These results demonstrate that the increased expression levels of Nav1.7, Nav1.8, and perhaps Nav1.1 in the Nf1+/- DRG make the largest contribution to the increased sodium current density and thus give rise to the enhanced excitability. Though the mechanisms by which many people with NF1 experience increased pain have not been elucidated, these abnormal painful states may involve elevated expression of specific sodium channel subtypes in small diameter nociceptive sensory neurons.

Original languageEnglish (US)
Pages (from-to)237-244
Number of pages8
JournalNeuroscience
Volume206
DOIs
StatePublished - Mar 29 2012

Keywords

  • Neurofibromin
  • QPCR
  • Sensory neuron

ASJC Scopus subject areas

  • Neuroscience(all)

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