Abstract
The tetrodotoxin-resistant voltage-gated sodium channel α-subunit Na v1.8 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 v1.8. To address this we have introduced human Na v1.8 in neuroblastoma SH-SY5Y cells. Voltage-clamp analysis showed that human Na v1.8 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 v1.8 was resistant to tetrodotoxin and activated by the pyrethroid toxin deltamethrin. Both voltage-activated and deltamethrin-activated human Na v1.8 were inhibited by the sodium channel blockers BIII 890 CL, NW-1029, and mexiletine. Inhibition of Na v1.8 by these compounds may underlie their known analgesic effects in animal models.
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