Cav3.2 T-type calcium channels control acute itch in mice

Cav3.2 T-type calcium channels control acute itch in mice
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DOI:
10.1186/s13041-020-00663-9
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发表时间:
2020-09-01
期刊:
影响因子:
3.6
通讯作者:
Zamponi, Gerald W.
Zamponi, Gerald W.
中科院分区:
医学3区
文献类型:
--
作者:
Gadotti, Vinicius M.;Kreitinger, Joanna M.;Zamponi, Gerald W.

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Cav3.2 T型钙通道是伤害性信号传导的重要介质,但其在瘙痒传导中的作用仍知之甚少。在这里,我们报告了这些通道作为瘙痒/瘙痒相关行为的关键调节剂的关键参与。我们比较了组胺或氯喹诱导的瘙痒模型中野生型和Cav3.2缺失小鼠之间的抓挠行为反应。我们还评估了T型钙通道阻滞剂DX 332在注射组胺或氯喹的雄性和雌性野生型小鼠中的作用。Cav3.2缺失小鼠在组胺和氯喹诱导的急性瘙痒期间表现出降低的抓挠反应。DX 332与致敏剂共注射抑制用组胺或氯喹处理的雄性和雌性小鼠的抓挠反应。总之,我们的数据提供了强有力的证据,Cav3.2 T型通道在调节初级感觉传入通路中的组胺依赖性和非依赖性瘙痒传递中发挥重要作用,并强调这些通道作为治疗瘙痒的潜在药理学靶点。
Cav3.2 T-type calcium channels are important mediators of nociceptive signaling, but their roles in the transmission of itch remains poorly understood. Here we report a key involvement of these channels as key modulators of itch/pruritus-related behavior. We compared scratching behavior responses between wild type and Cav3.2 null mice in models of histamine- or chloroquine-induced itch. We also evaluated the effect of the T-type calcium channel blocker DX332 in male and female wild-type mice injected with either histamine or chloroquine. Cav3.2 null mice exhibited decreased scratching responses during both histamine- and chloroquine-induced acute itch. DX332 co-injected with the pruritogens inhibited scratching responses of male and female mice treated with either histamine or chloroquine. Altogether, our data provide strong evidence that Cav3.2 T-type channels exert an important role in modulating histamine-dependent and -independent itch transmission in the primary sensory afferent pathway, and highlight these channels as potential pharmacological targets to treat pruritus.