Augmented sodium currents contribute to the enhanced excitability of small diameter capsaicin-sensitive sensory neurons isolated from Nf1+/- mice

Yue Wang, J. H. Duan, C. M. Hingtgen, G. D. Nicol

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Abstract

Neurofibromin, the product of the Nf1 gene, is a guanosine triphosphatase activating protein (GAP) for p21ras (Ras) that accelerates conversion of active Ras-GTP to inactive Ras-GDP. Sensory neurons with reduced levels of neurofibromin likely have augmented Ras-GTP activity. We reported previously that sensory neurons isolated from a mouse model with a heterozygous mutation of the Nf1 gene (Nf1+/-) exhibited greater excitability compared with wild-type mice. To determine the mechanism giving rise to the augmented excitability, differences in specific membrane currents were examined. Consistent with the enhanced excitability of Nf1+/- neurons, peak current densities of both tetrodotoxin-resistant sodium current (TTX-R INa) and TTX-sensitive (TTX-S) INa were significantly larger in Nf1+/- than in wild-type neurons. Although the voltages for half-maximal activation (V0.5) were not different, there was a significant depolarizing shift in the V 0.5 for steady-state inactivation of both TTX-R and TTX-S I Na in Nf1+/- neurons. In addition, levels of persistent I Na were significantly larger in Nf1+/-neurons. Neither delayed rectifier nor A-type potassium currents were altered in Nf1+/- neurons. These results demonstrate that enhanced production of action potentials in Nf1+/- neurons results, in part, from larger current densities and a depolarized voltage dependence of steady-state inactivation for INa that potentially leads to a greater availability of sodium channels at voltages near the firing threshold for the action potential.

Original languageEnglish (US)
Pages (from-to)2085-2094
Number of pages10
JournalJournal of Neurophysiology
Volume103
Issue number4
DOIs
StatePublished - Apr 1 2010

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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