Pain Perception in Mice Lacking the β3 Subunit of Voltage-activated Calcium Channels*-猫眼课题宝

缺乏电压激活钙通道 β3 亚基的小鼠的疼痛感知*

DOI：

发表时间：

2002

期刊：

Journal of Biological Chemistry

影响因子：

4.8

通讯作者：

中科院分区：

生物学2区

文献类型：

作者：

M. Murakami;B. Fleischmann;C. de Felipe;M. Freichel;C. Trost;A. Ludwig;U. Wissenbach;H. Schwegler;F. Hofmann;J. Hescheler;V. Flockerzi;A. Cavalié

N型和P/Q型钙通道阻滞剂的脊髓抗伤害性作用以及α1B亚基（N型）的基因靶向作用表明电压激活钙通道在疼痛处理中的重要性。在神经元中，钙通道的辅助β3亚基优先与α1B亚基结合。在这里，我们表明，通过基因打靶删除β3亚基强烈影响突变小鼠的疼痛处理。我们在体内脊髓的疼痛相关行为和上行疼痛通路以及体外单个背根神经节神经元的钙通道电流和蛋白水平上确定了这种缺陷。由化学炎症诱导的疼痛优先通过缺失β3亚基而减弱，而对急性热和机械有害刺激的反应分别中度降低或完全不降低。该缺陷导致在强烈的传入神经刺激期间脊髓活动的弱卷绕。其分子机制与N型钙通道（α1B）的低表达和脊髓投射神经元钙通道电流的功能改变有关。

The importance of voltage-activated calcium channels in pain processing has been suggested by the spinal antinociceptive action of blockers of N- and P/Q-type calcium channels as well as by gene targeting of the α1B subunit (N-type). The accessory β3 subunits of calcium channels are preferentially associated with the α1B subunit in neurones. Here we show that deletion of the β3 subunit by gene targeting affects strongly the pain processing of mutant mice. We pinpoint this defect in the pain-related behavior and ascending pain pathways of the spinal cordin vivo and at the level of calcium channel currents and proteins in single dorsal root ganglion neurones in vitro. The pain induced by chemical inflammation is preferentially damped by deletion of β3 subunits, whereas responses to acute thermal and mechanical harmful stimuli are reduced moderately or not at all, respectively. The defect results in a weak wind-up of spinal cord activity during intense afferent nerve stimulation. The molecular mechanism responsible for the phenotype was traced to low expression of N-type calcium channels (α1B) and functional alterations of calcium channel currents in neurones projecting to the spinal cord.

beta subunits influence the biophysical and pharmacological differences between P- and Q-type calcium currents expressed in a mammalian cell line.