Modulation of sensory neuron potassium conductances by anandamide indicates roles for metabolites
Modulation of sensory neuron potassium conductances by anandamide indicates roles for metabolites
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DOI：
10.1038/bjp.2008.93
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发表时间：
2008-05-01
影响因子：
7.3
通讯作者：
Scott, R. H.
中科院分区：
文献类型：
--
作者：
Evans, R. M.;Wease, K. N.;Scott, R. H.
背景与目的：内源性大麻素大麻酰胺（AEA）作用于大麻素（CB（1））和香草素（TRPV（1））受体。AEA也显示出抗伤害感受特性;尽管其潜在机制尚未完全了解，但CB（1）和TRPV（1）都可能参与其中。AEA对培养的大鼠背根神经节（DRG）神经元电压激活性Ca（2+）通道的调节作用。然而，AEA在不同群体的神经元中增强或减弱KCl诱发的Ca（2+）内流;这些效应与索马的大小有关。实验方法：采用全细胞膜片钳技术和Fura-2 Ca（2+）成像技术研究AEA对动作电位放电和电压激活的K（+）电流的影响，并探讨AEA的代谢在其对培养DRG神经元的作用中是否起作用。AEA减弱了DRG神经元亚群中由300 ms去极化电流命令诱发的多个动作电位放电。应用1 μ M AEA减弱电压激活的K（+）电流和KCl诱发的Ca（2+）瞬变的恢复。这些反应对CB（1）受体拮抗剂利莫那班（100 nM）和用百日咳毒素预孵育DRG神经元不敏感，表明这些作用不是CB（1）受体介导的。用脂肪酸酰胺水解酶（FAAH）抑制剂苯甲基磺酰氟（PMSF）预孵育DRG神经元，可减弱AEA对K（+）电流和Ca（2+）内流的抑制作用.结论和意义：FAAH代谢AEA的产物参与了培养感觉神经元K（+）电导的减弱和兴奋性的改变.
Background and purpose: The endogenous cannabinoid anandamide (AEA) acts at cannabinoid (CB(1)) and vanilloid (TRPV(1)) receptors. AEA also shows antinociceptive properties; although the underlying mechanism for this is not fully understood, both CB(1) and TRPV(1) may be involved. Voltage-activated Ca(2+) channels in rat-cultured dorsal root ganglion (DRG) neurons are modulated by AEA. However, AEA in different populations of neurons enhanced or attenuated KCl-evoked Ca(2+) influx; these effects were linked with soma size. The aim of this study was to determine how AEA or its metabolites might produce these variable responses.Experimental approach: The whole cell patch-clamp technique and fura-2 Ca(2+) imaging were used to characterize the actions of AEA on action potential firing and voltage-activated K(+) currents and to determine whether AEA metabolism plays any role in its effects on cultured DRG neurons.Key results: AEA attenuated multiple action potential firing evoked by 300 ms depolarizing current commands in a subpopulation of DRG neurons. Application of 1 mu M AEA attenuated voltage-activated K(+) currents and the recovery of KCl-evoked Ca(2+) transients. The insensitivity of these responses to the CB(1) receptor antagonist rimonabant (100 nM) and preincubation of DRG neurons with pertussis toxin suggested that these actions are not CB(1) receptor-mediated. Preincubating DRG neurons with the fatty acid amide hydrolase (FAAH) inhibitor phenylmethylsulphonyl fluoride (PMSF) attenuated the inhibitory actions of AEA on K(+) currents and Ca(2+) influx.Conclusion and implications: These data suggest that the products of AEA metabolism by FAAH contribute to the attenuation of K(+) conductances and altered excitability of cultured sensory neurons.