Sensory neuron sodium channel Nov1.8 is essential for pain at low temperatures (Nature 2007, 447:855-858)

報告日期: 2008/06/13
報告時間: 16:00/16:50
報告學生: 吳智陽
講評老師: 吳豐森
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/970613-2.pdf

Sensory neuron sodium channel Nav1.8 is essential for pain

at low temperatures

Nature, 447, 855-859, 2007

Speaker︰吳智陽

Commentator吳豐森老師

Time2008/6/13 16:10-17:00

PlaceRoom 602

Abstract

Nociceptors are peripheral sensory neurons that respond to stimuli which are capable of producing tissue damage and pain.  These sensory neurons express several voltage-gated sodium channels (VGSCs) a-subunits, with fast (for example Nav1.7) or slow (Nav1.8 and Nav1.9) kinetics 1, 2.  By using tetrodotoxin (TTX) as a tool to detect action potentials generation in intact nociceptive terminals, the authors wanted to define the conditions under which these channels become physiologically relevant as an impulse generator.  They found that Nav1.8 channel is essential for sustained excitability of nociceptors when the skin is cooled (10 0C) relative to high temperature (30 0C).  The data are also shown that cooling excitable membranes progressively enhances the voltage-dependent slow inactivation of TTX-sensitive VGSCs and the inactivation properties of Nav1.8 are entirely cold-resistant.  The low temperatures (10 0C) also decrease the activation threshold of the sodium currents and increase the membrane resistance, augmenting the voltage change caused by any membrane current.  Furthermore, in the cold condition, Nav1.8 remains available as the sole electrical impulse generator in nociceptors that transmits nociceptive information to the central nervous system.  Consistent with this concept is the observation that Nav1.8-null mutant mice show negligible responses to noxious cold and mechanical stimulation at low temperatures.  The authors present strong evidence for a specialized role of Nav1.8 in nociceptors as the critical channel which function for the perception of cold pain and pain in the cold.

 

Reference

1.     Akopian, A. N., Sivilotti, L. & Wood, J. N. A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. Nature 379, 257–262 (1996).

2.     Dib-Hajj, S., Black, J. A., Cummins, T. R. & Waxman, S. G. NaN/Nav1.9: a sodium channel with unique properties. Trends Neurosci. 25, 253–259 (2002).