Does the Altered Expression of Ion Channels Give Rise to the Enhanced Excitability of Neurons Isolated from Nf1 +/- Mice?
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 to 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 PCR was used to measure expression levels of the nine different voltage-gated sodium channel alpha subunits and the four associated auxiliary 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 beta 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 beta subunits, B1 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2011
- Accession Number
- ADA560794
Entities
People
- Grant Nicol
Organizations
- Indiana University Bloomington