Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, 5 Poniente 1670, Talca 3460000, Chile.
Centro de Investigaciones Médicas, Programa de Investigación Asociativa en Cáncer Gástrico, Escuela de Medicina, Universidad de Talca, Talca 3460000, Chile.
Molecules. 2018 Aug 21;23(9):2094. doi: 10.3390/molecules23092094.
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are highly regulated proteins which respond to different cellular stimuli. The HCN currents (I) mediated by HCN1 and HCN2 drive the repetitive firing in nociceptive neurons. The role of HCN channels in pain has been widely investigated as targets for the development of new therapeutic drugs, but the comprehensive design of HCN channel modulators has been restricted due to the lack of crystallographic data. The three-dimensional structure of the human HCN1 channel was recently reported, opening new possibilities for the rational design of highly-selective HCN modulators. In this review, we discuss the structural and functional properties of HCN channels, their pharmacological inhibitors, and the potential strategies for designing new drugs to block the HCN channel function associated with pain perception.
超极化激活环核苷酸门控（HCN）通道是高度调节的蛋白质，可响应不同的细胞刺激。由 HCN1 和 HCN2 介导的 HCN 电流（I）驱动伤害感受神经元的重复放电。HCN 通道在疼痛中的作用已被广泛研究，作为开发新治疗药物的靶点，但由于缺乏晶体学数据，HCN 通道调节剂的综合设计受到限制。最近报道了人 HCN1 通道的三维结构，为高选择性 HCN 调节剂的合理设计开辟了新的可能性。在这篇综述中，我们讨论了 HCN 通道的结构和功能特性、它们的药理学抑制剂以及设计新药物以阻断与疼痛感知相关的 HCN 通道功能的潜在策略。
