Park Seo-In, Hwang Soobeen, Lee Young, Lee Hee-Yoon, Kim Soohyun, Hong Junseo, Jo Su-Hyun, Choi Se-Young
Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, 03080, Republic of Korea.
Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 24341, Republic of Korea.
Mol Brain. 2025 May 8;18(1):41. doi: 10.1186/s13041-025-01211-z.
Kv1.3 channels in microglia are pivotal in regulating neuroinflammation. The antipsychotic chlorpromazine (CPZ) demonstrates anti-inflammatory effects by decreasing Kv1.3 activity in mPFC microglia. However, the precise mechanism of CPZ's effect in the mPFC remains unclear, given that CPZ is known to inhibit dopamine receptors and the mPFC contains various cell types with dopamine receptors. In this study, we investigate how CPZ inhibits Kv1.3 channels using human Kv1.3 channel-expressing Xenopus laevis oocytes. CPZ directly inhibits Kv1.3 channel currents in a concentration-dependent manner. The CPZ-mediated Kv1.3 channel inhibition is not voltage-dependent, and CPZ accelerates Kv1.3 channel inactivation without significantly affecting its activation. Our findings suggest that CPZ directly blocks Kv1.3 channels without involving other ion channels or receptors, including dopamine receptors, thereby contributing to the understanding of its neuroinflammation-suppressing mechanism.
小胶质细胞中的Kv1.3通道在调节神经炎症中起关键作用。抗精神病药物氯丙嗪（CPZ）通过降低内侧前额叶皮质（mPFC）小胶质细胞中的Kv1.3活性表现出抗炎作用。然而，鉴于已知CPZ可抑制多巴胺受体且mPFC包含多种具有多巴胺受体的细胞类型，CPZ在mPFC中的作用的确切机制仍不清楚。在本研究中，我们使用表达人Kv1.3通道的非洲爪蟾卵母细胞来研究CPZ如何抑制Kv1.3通道。CPZ以浓度依赖性方式直接抑制Kv1.3通道电流。CPZ介导的Kv1.3通道抑制不依赖电压，并且CPZ加速Kv1.3通道失活而不显著影响其激活。我们的研究结果表明，CPZ直接阻断Kv1.3通道，而不涉及其他离子通道或受体，包括多巴胺受体，从而有助于理解其神经炎症抑制机制。
