PDF(Pubmed)
Abstract：
Enhanced electrical activity in detrusor smooth muscle (DSM) cells is a key factor in detrusor overactivity which causes overactive bladder pathological disorders. Transient receptor potential melastatin-4 (TRPM4) channels, which are calcium-activated cation channels, play a role in regulating DSM electrical activities. These channels likely contribute to depolarizing the DSM cell membrane, leading to bladder overactivity. Our research focuses on understanding TRPM4 channel function in the DSM cells of mice, using computational modeling. We aimed to create a detailed computational model of the TRPM4 channel based on existing electrophysiological data. We employed a modified Hodgkin-Huxley model with an incorporated TRP-like current to simulate action potential firing in response to current and synaptic stimulus inputs. Validation against experimental data showed close agreement with our simulations. Our model is the first to analyze the TRPM4 channel\'s role in DSM electrical activity, potentially revealing insights into bladder overactivity. In conclusion, TRPM4 channels are pivotal in regulating human DSM function, and TRPM4 channel inhibitors could be promising targets for treating overactive bladder.
摘要：
逼尿肌平滑肌(DSM)细胞电活动增强是导致膀胱过度活动症的关键因素。瞬时受体电位-4（TRPM4）通道，它们是钙激活的阳离子通道，在调节DSM电气活动中发挥作用。这些通道可能有助于使DSM细胞膜去极化，导致膀胱过度活动.我们的研究重点是了解小鼠DSM细胞中TRPM4通道的功能，使用计算建模。我们旨在基于现有的电生理数据创建TRPM4通道的详细计算模型。我们采用了改良的Hodgkin-Huxley模型，其中包含类似TRP的电流，以模拟响应电流和突触刺激输入的动作电位激发。对实验数据的验证显示与我们的模拟非常吻合。我们的模型是第一个分析TRPM4通道在DSM电活动中的作用的模型，可能揭示膀胱过度活动的见解。总之,TRPM4通道在调节人类DSM功能方面至关重要，TRPM4通道抑制剂可能是治疗膀胱过度活动症的有希望的靶点。
