Analysis of human Nav1.8 expressed in SH-SY5Y neuroblastoma cells
Analysis of human Nav1.8 expressed in SH-SY5Y neuroblastoma cells
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DOI：
10.1016/j.ejphar.2005.10.035
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发表时间：
2005-12-28
影响因子：
5
通讯作者：
James, LF
中科院分区：
文献类型：
--
作者：
Dekker, LV;Daniels, Z;James, LF
The tetrodotoxin-resistant voltage-gated sodium channel alpha-subunit Na(v)1.8 is expressed in nociceptors and has been implicated in chronic pain. Difficulties of heterologous expression have so far precluded analysis of the pharmacological properties of human Na(v)1.8. To address this we have introduced human Na(v)1.8 in neuroblastoma SH-SY5Y cells. Voltage-clamp analysis showed that human Nav 1.8 generated an inward tetrodotoxin-resistant sodium current with an activating threshold around - 50 mV, half maximal activation at - 11 +/- 3 mV and a reversal potential of 67 +/- 4 mV. These properties closely match those of the endogenous rat tetrodotoxin-resistant sodium current in dorsal root ganglia suggesting that the expressed human channel is in a near physiological conformation. Human Na(v)1.8 was resistant to tetrodotoxin and activated by the pyrethroid toxin deltamethrin. Both voltage-activated and deltamethrin-activated human Na(v)1.8 were inhibited by the sodium channel blockers BIII 890 CL, NW-1029, and mexiletine. Inhibition of Na(v)1.8 by these compounds may underlie their known analgesic effects in animal models. (c) 2005 Elsevier B.V. All rights reserved.
