Ca V 3.2 calcium channels: new players in facial pain.
Ca V 3.2 calcium channels: new players in facial pain.
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DOI：
10.1097/j.pain.0000000000002652
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发表时间：
2022-12-01
期刊：
影响因子：
7.4
通讯作者：
中科院分区：
文献类型：
--
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三叉神经痛是最常见的神经性疼痛类型，涉及颅面区域。三叉神经痛是指三叉神经的一个或多个分支突然和短暂反复发作的刺痛。13最近的研究将三叉神经痛与电压门控钙通道功能障碍联系起来。例如，CACNA 1A（CaV 2. 1或P/Q型电压门控钙通道）变体（P2455 H）在三叉神经痛患者中报告3，并导致通道活性的功能获得（GoF）和功能丧失（LoF），6表明CaV 2的相关变化。三叉神经系统中的1功能可能有助于三叉神经痛的发展。在CACNA 1H（即CaV 3。2 T型电压门控钙通道），19破坏性的变体已被预测;然而，迄今为止，没有研究已经专门调查任何这些CaV 3的功能作用。三叉神经痛的2种通道变异。在最新一期的《疼痛》杂志中，Gambeta等7阐述了这一知识缺口。利用电生理记录，生物化学和动物行为测定，作者发现了CaV 3的新作用。2三叉神经口面疼痛综合征。2通道与疼痛超敏反应有关，1大多数研究都集中在这些通道在许多炎症和神经病理性疼痛模型中调节背根神经节和脊髓背角神经元兴奋性的作用。1在这项研究中，作者表明，CaV 3.与人类三叉神经痛相关的2个错义突变影响重组CaV 3的功能活性。2通道在人胚肾细胞中表达。在Dong等人报道的19种CACNA 1H突变中，4选择了4种变体用于本研究及其对CaV 3生物物理性质的影响。使用外显子26（人）或25（小鼠）变体询问2个通道。一个突变（E286 K）位于结构域I的孔环内，其他3个突变（H526 Y、G563 R和P566 T）位于通道的胞内环I-II内（图1A、B）。在分析的4种突变中，其中2种（G563 R和P566 T）产生宏观CaV 3的显著增加。2 Ca 21电流，与通道变体的GoF一致。相比之下，E286 K突变导致轻微的LoF，而H526 Y突变没有观察到变化。观察到的效果是独立的表达水平的通道在膜上。这些结果提出了一个问题，即两种相反的机制-LoF和
Trigeminal neuralgia is the most common type of neuropathic pain involving the craniofacial region. Trigeminal neuralgia is defined as sudden and brief recurrent episodes of stabbing pain in one or more branches of the trigeminal nerve. 13 Recent studies have linked trigeminal neuralgia to dysfunctions in voltage-gated calcium channels. 3, 4 For instance, a CACNA1A (CaV2. 1 or P/Q-type voltage-gated calcium channel) variant (P2455H) was reported in a patient with trigeminal neuralgia3 and caused both gain of function (GoF) and loss of function (LoF) of the channels’ activity, 6 suggesting that associated changes in CaV2. 1 function in the trigeminal system may contribute to the development of trigeminal neuralgia. In CACNA1H (ie, the CaV3. 2 T-type voltagegated calcium channel), 19 damaging variants have been predicted; however, no study to date has specifically investigated the functional role of any of these CaV3. 2 channel variants in trigeminal neuralgia. In the current issue of PAIN, Gambeta et al. 7 address this gap in knowledge. Using electrophysiological recordings, biochemistry, and animal behavior assays, the authors uncovered a novel role of CaV3. 2 in trigeminal orofacial pain syndromes.Although CaV3. 2 channels have been implicated in pain hypersensitivity, 1 most of this research has centered around the roles of these channels in regulating dorsal root ganglia and spinal dorsal horn neuron excitability in numerous inflammatory and neuropathic pain models. 1 In this study, the authors show that CaV3. 2 missense mutations linked to trigeminal neuralgia in humans affect the functional activity of recombinant CaV3. 2 channels expressed in human embryonic kidney cells. Of the 19 CACNA1H mutations reported by Dong et al., 4 4 variants were selected for this study and their effect on the biophysical properties of CaV3. 2 channels were interrogated using the exon 26 (human) or 25 (mouse) variant. One mutation (E286K) is located within the pore loop of domain I, and the other 3 mutations (H526Y, G563R, and P566T) are in the intracellular loop I-II of the channel (Fig. 1A, B). Among the 4 mutations analyzed, 2 of them (G563R and P566T) produced a significant increase in macroscopic CaV3. 2 Ca21 currents, consistent with a GoF of the channel’s variants. By contrast, the E286K mutation resulted in a slight LoF, while no changes were seen with the H526Y mutation. The observed effects were independent of the expression level of the channels at the membrane. These results raise the question of how 2 opposite mechanisms—LoF and
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
5.3
作者：
Gomez, Kimberly;Calderon-Rivera, Aida;Felix, Ricardo
通讯作者：
Felix, Ricardo
影响因子：
3.6
作者：
Gambeta E;Gandini MA;Souza IA;Ferron L;Zamponi GW
通讯作者：
Zamponi GW
影响因子：
64.8
作者：
Zhao, Yanyu;Huang, Gaoxingyu;Yan, Nieng
通讯作者：
Yan, Nieng
神经损伤提升浅表脊髓背角的功能性 Cav3.2 通道
影响因子：
3.3
作者：
Feng, Xiao-Jin;Ma, Long-Xian;Liu, Tao
通讯作者：
Liu, Tao