Binzen U, Greffrath W, Hennessy S, Bausen M, Saaler-Reinhardt S, Treede R-D
Institute of Physiology and Pathophysiology, Johannes Gutenberg-University, Saarstrasse 21, D-55099, Mainz, Germany.
Neuroscience. 2006 Oct 13;142(2):527-39. doi: 10.1016/j.neuroscience.2006.06.020. Epub 2006 Aug 4.
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.
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。