Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA.
Eur J Neurosci. 2010 Apr;31(7):1219-32. doi: 10.1111/j.1460-9568.2010.07156.x. Epub 2010 Mar 19.
Neuromodulators, such as substance P (SubP), play an important role in modulating many rhythmic activities driven by central pattern generators (e.g. locomotion, respiration). However, the mechanism by which SubP enhances breathing regularity has not been determined. Here, we used mouse brainstem slices containing the pre-Bötzinger complex to demonstrate, for the first time, that SubP activates transient receptor protein canonical (TRPC) channels to enhance respiratory rhythm regularity. Moreover, SubP enhancement of network regularity is accomplished via selective enhancement of ICAN (inward non-specific cation current)-dependent intrinsic bursting properties. In contrast to INaP (persistent sodium current)-dependent pacemakers, ICAN-dependent pacemaker bursting activity is TRPC-dependent. Western Blots reveal TRPC3 and TRPC7 channels are expressed in rhythmically active ventral respiratory group island preparations. Taken together, these data suggest that SubP-mediated activation of TRPC3/7 channels underlies rhythmic ICAN-dependent pacemaker activity and enhances the regularity of respiratory rhythm activity.
神经调质，如 P 物质（SubP），在调节由中枢模式发生器驱动的许多节律活动方面发挥着重要作用（例如，运动、呼吸）。然而，SubP 增强呼吸节律规则性的机制尚未确定。在这里，我们使用包含前脑桥复合体的小鼠脑切片，首次证明 SubP 通过激活瞬时受体蛋白经典（TRPC）通道来增强呼吸节律规则性。此外，SubP 通过选择性增强 ICAN（内向非特异性阳离子电流）依赖性内在爆发特性来增强网络规则性。与 INaP（持续钠电流）依赖性起搏器不同，ICAN 依赖性起搏器爆发活动依赖于 TRPC。Western Blots 显示 TRPC3 和 TRPC7 通道在节律性活跃的腹侧呼吸组岛制剂中表达。综上所述，这些数据表明，SubP 介导的 TRPC3/7 通道的激活是节律性 ICAN 依赖性起搏器活动的基础，并增强了呼吸节律活动的规则性。
