膀胱过度活动症（OAB）严重影响患者生活，是临床上发病机制不清且又最缺乏有效治疗手段的一类疾病。膀胱感觉信号的异常是引发OAB的重要因素。离子通道的病变可能通过影响感觉细胞膜电位及兴奋性引起膀胱感觉信号异常并引发OAB症状。超极化激活环核苷酸门控阳离子通道(HCN)与膀胱感觉信号通路密切相关。在前一项国科金青年项目资助下，我们发现OAB大鼠膀胱感觉信号传递通路中的关键细胞膀胱间质细胞及脊髓背根节神经元中HCN4通道表达明显上调。但HCN4通道如何参与OAB膀胱异常感觉信号传递尚不清楚。基于此，我们拟采用形态学、分子生物学、全细胞膜片钳及膀胱感觉神经电生理等技术，观察OAB大鼠膀胱间质细胞及背根节神经元内HCN4通道的生物物理特性、调制机制及其可塑性变化，明确HCN4通道在OAB膀胱异常感觉信号传递的作用及调控机制，为进一步了解OAB的发病新机制，寻找新的OAB药物作用靶点提供实验基础。

Overactive bladder (OAB) is a prevalent and chronic medical condition that greatly impacts an individual's QOL, while the multifactorial pathophysiology of this condition and intrinsic compensatory mechanisms confound the evaluation of treatment response. Dysfunction of bladder afferent signaling has been proposed to contribute to the pathogenesis of OAB. Ion channel disorders may lead to the dysfunction of afferent signaling and induce OAB symptom through affecting afferent cell membrane potential and excitability. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been shown to play key roles in bladder afferent signaling. Surpported from the former National Natural Science Foundation, our pilot study revealed the upregulation of expression of HCN4 channels in OAB rat bladder interstitial cells (ICC) and dorsal root ganglion (DRG) neurons. And these cells play key roles in the bladder afferent signaling. However, the mechanisms underlying HCN4 channels in the dysfunction of bladder afferent signaling remain unclear. In this project, multiple experimental techniques, including morphology, molecular biology, whole cell patch clamp and afferent nerve electrophysiology will be employed. And we aim to investigate the functions and modulation mechanisms of HCN4 channels in afferent signaling in OAB, through investigation of the bio-physiologic feature, regulation effects and plasticity changes of HCN4 channels in bladder ICC and DRG neurons in OAB rats. Furthermore, this study might provide experimental basis for understanding the etiology and exploring more effective novel drug targets for OAB treatment.