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电压门控钾通道Kv1.4与瞬时受体电位通道(TRPV1和TRPV2)以及大麻素受体CB1在大鼠背根神经节神经元中的共表达。

Co-expression of the voltage-gated potassium channel Kv1.4 with transient receptor potential channels (TRPV1 and TRPV2) and the cannabinoid receptor CB1 in rat dorsal root ganglion neurons.

作者信息

Binzen U, Greffrath W, Hennessy S, Bausen M, Saaler-Reinhardt S, Treede R-D

机构信息

Institute of Physiology and Pathophysiology, Johannes Gutenberg-University, Saarstrasse 21, D-55099, Mainz, Germany.

出版信息

Neuroscience. 2006 Oct 13;142(2):527-39. doi: 10.1016/j.neuroscience.2006.06.020. Epub 2006 Aug 4.

Abstract

Potassium channels contribute to basic neuronal excitability and modulation. Here, we examined expression patterns of the voltage-gated potassium channel Kv1.4, the nociceptive transduction channels TRPV1 and TRPV2 as well as the putative anti-nociceptive cannabinoid receptor CB1 by immunofluorescence double-labelings in sections of rat dorsal root ganglia (DRGs). Kv1.4, TRPV1 and CB1 were each detected in about one third of neurons (35.7+/-0.5%, 29.4+/-1.1% and 36.4+/-0.5%, respectively, mean diameter 19.1+/-0.3 microm). TRPV2 was present in 4.4+/-0.4% of all neurons that were significantly larger in diameter (27.4+/-0.7 microm; P < 0.001). Antibody double-labeling revealed that the majority of Kv1.4-positive neurons co-expressed TRPV1 (73.9+/-1.5%) whereas none expressed TRPV2. The largest overlap was found with CB1 (93.1+/-0.1%). CB1 expression resembled that seen for Kv1.4 since the majority of neurons expressing CB1-protein also expressed TRPV1 (69.4+/-6.5%) but not TRPV2 (0.6+/-0.3%). When CB1-mRNA was detected using in situ hybridizations an additional subset of larger neurons was labeled including 82.4+/-17.7% of the TRPV2 expressing neurons. However, co-localization of Kv1.4 with CB1-mRNA (92%, mean diameter: 18.5 microm) was essentially the same as with CB1-protein. The almost complete overlap of CB1 and Kv1.4 in nociceptive DRG neurons suggests a functional synergistic action between Kv1.4 and CB1. The potassium channel may have two important roles in nociception. As the molecular basis of A-type current it could be involved in the control of repetitive discharges at peripheral terminals and as a downstream signal transduction site of CB1 in the control of presynaptic transmitter release at central terminals.

摘要

钾通道对神经元的基本兴奋性和调节起着重要作用。在此,我们通过免疫荧光双标法检测了大鼠背根神经节(DRG)切片中电压门控钾通道Kv1.4、伤害性转导通道TRPV1和TRPV2以及假定的抗伤害性大麻素受体CB1的表达模式。Kv1.4、TRPV1和CB1分别在约三分之一的神经元中被检测到(分别为35.7±0.5%、29.4±1.1%和36.4±0.5%,平均直径19.1±0.3微米)。TRPV2存在于所有神经元的4.4±0.4%中,这些神经元的直径明显更大(27.4±0.7微米;P<0.001)。抗体双标显示,大多数Kv1.4阳性神经元共表达TRPV1(73.9±1.5%),而无一表达TRPV2。与CB1的重叠最大(93.1±0.1%)。CB1的表达与Kv1.4相似,因为大多数表达CB1蛋白的神经元也表达TRPV1(69.4±6.5%),但不表达TRPV2(0.6±0.3%)。当使用原位杂交检测CB1-mRNA时,标记了另一组较大的神经元,包括82.4±17.7%表达TRPV2的神经元。然而,Kv1.4与CB1-mRNA的共定位(92%,平均直径:18.5微米)与与CB1蛋白的共定位基本相同。CB1和Kv1.4在伤害性DRG神经元中的几乎完全重叠表明Kv1.4和CB1之间存在功能协同作用。钾通道在伤害感受中可能有两个重要作用。作为A型电流的分子基础,它可能参与控制外周终末的重复放电,并作为CB1的下游信号转导位点,在控制中枢终末的突触前递质释放中发挥作用。

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