Augmented Sodium Currents Contribute to the Enhanced Excitability of Small Diameter Capsaicin-Sensitive Sensory Neurons Isolated From Nf1+/- Mice

作者：Wang Yue; Duan J H; Hingtgen C M; Nicol G D^*

来源：Journal of Neurophysiology, 2010, 103(4): 2085-2094.

DOI：10.1152/jn.01010.2009

Wang Y, Duan JH, Hingtgen CM, Nicol GD. Augmented sodium currents contribute to the enhanced excitability of small diameter capsaicin-sensitive sensory neurons isolated from Nf1+/- mice. J Neurophysiol 103: 2085-2094, 2010. First published February 17, 2010; doi: 10.1152/jn.01010.2009. 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 I(Na)) and TTX-sensitive (TTX-S) I(Na) were significantly larger in Nf1+/- than in wild-type neurons. Although the voltages for half-maximal activation (V(0.5)) 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 I(Na) that potentially leads to a greater availability of sodium channels at voltages near the firing threshold for the action potential.

• 出版日期2010-4