Drew Liam J, Wood John N
Dept, of Biology, UCL, Gower Street, London, WC1E 6BT, UK.
Mol Pain. 2007 Jan 6;3:1. doi: 10.1186/1744-8069-3-1.
The molecular identity and pharmacological properties of mechanically gated ion channels in sensory neurons are poorly understood. We show that FM1-43, a styryl dye used to fluorescently label cell membranes, permeates mechanosensitive ion channels in cultured dorsal root ganglion neurons, resulting in blockade of three previously defined subtypes of mechanically activated currents. Blockade and dye uptake is voltage dependent and regulated by external Ca2+. The structurally related larger dye FM3-25 inhibited mechanically activated currents to a lesser degree and did not permeate the channels. In vivo, FMI-43 decreases pain sensitivity in the Randall-Selitto test and increases the withdrawal threshold from von Frey hairs, together suggesting that the channels expressed at the cell body in culture mediate mechanosensation in the intact animal. These data give further insight into the mechanosensitive ion channels expressed by somatosensory neurons and suggest FM dyes are an interesting tool for studying them.
感觉神经元中机械门控离子通道的分子特性和药理特性目前了解甚少。我们发现,用于对细胞膜进行荧光标记的苯乙烯基染料FM1-43可透过培养的背根神经节神经元中的机械敏感离子通道,从而阻断三种先前定义的机械激活电流亚型。阻断和染料摄取依赖于电压,并受细胞外Ca2+调节。结构相关的较大染料FM3-25对机械激活电流的抑制作用较小,且不能透过通道。在体内,FM1-43在Randall-Selitto试验中降低疼痛敏感性,并提高对von Frey毛发的撤换阈值,这共同表明培养物中细胞体表达的通道介导完整动物的机械感觉。这些数据进一步深入了解了躯体感觉神经元表达的机械敏感离子通道,并表明FM染料是研究它们的一个有趣工具。