Comparison of the pharmacological properties of rat Na(V)1.8 with rat Na(V)1.2a and human Na(V)1.5 voltage-gated sodium channel subtypes using a membrane potential sensitive dye and FLIPR.

Receptors & channels Pub Date : 2004-01-01

R G Vickery, S M Amagasu, R Chang, N Mai, E Kaufman, J Martin, J Hembrador, M D O'Keefe, C Gee, D Marquess, J A M Smith

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Abstract

A novel, membrane potential sensitive dye and a fluorescence imaging plate reader (FLIPR) have been used to characterize the pharmacological properties of rat Na(v)1.8 voltage-gated sodium channels (VGSC) in parallel with rat Na(v)1.2a and human Na(v)1.5 VGSC subtypes, respectively. The sensitivity of recombinant Na(v)1.2a-CHO, Na(v)1.5-293-EBNA, and Na(v)1.8-F-11 cells to VGSC activators was subtype dependent. Veratridine evoked depolarization of Na(v)1.2a-CHO and Na(v)1.5-293-EBNA cells with pEC(50) values of 4.78 +/- 0.13 and 4.84 +/- 0.12, respectively (n = 3), but had negligible effect on Na(v)1.8-F-11 cells (pEC(50) < 4.5). Type I pyrethroids were without significant effect at all subtypes. In contrast, the type II pyrethroids deltamethrin and fenvalerate evoked direct depolarization of Na(v)1.8-F-11 and Na(v)1.5-293-EBNA cells. Deltamethrin potentiated the veratridine-evoked response in Na(v)1.8-F-11 cells by > or =20-fold, in contrast to a

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利用膜电位敏感染料和FLIPR比较大鼠Na(V)1.8与大鼠Na(V)1.2a和人Na(V)1.5电压门控钠通道亚型的药理学性质。

利用一种新型的膜电位敏感染料和荧光成像板阅读器(FLIPR)分别表征了大鼠Na(v)1.8电压门控钠通道(VGSC)与大鼠Na(v)1.2a和人Na(v)1.5 VGSC亚型的药理学性质。重组Na(v)1.2a-CHO、Na(v)1.5-293-EBNA和Na(v)1.8-F-11细胞对VGSC激活剂的敏感性呈亚型依赖性。Veratridine对Na(v)1.2a-CHO和Na(v)1.5-293-EBNA细胞的去极化作用分别为pEC(50)值4.78 +/- 0.13和4.84 +/- 0.12 (n = 3)，对Na(v)1.8-F-11细胞的去极化作用可忽略(pEC(50) < 4.5)。I型拟除虫菊酯对所有亚型均无显著影响。II型拟除虫菊酯类杀虫剂溴氰菊酯和氰戊菊酯诱导Na(v)1.8-F-11和Na(v)1.5-293-EBNA细胞直接去极化。溴氰菊酯能使Na(v)1.8-F-11细胞的缬草碱诱发反应增强>或=20倍

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Receptors & channels

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