Mañé Noemí, Gil Víctor, Martínez-Cutillas Míriam, Martín María Teresa, Gallego Diana, Jiménez Marcel
Pflugers Arch. 2014 Dec;466(12):2305-21. doi: 10.1007/s00424-014-1500-8.
Interaction of different neuromyogenic mechanisms determines colonic motility. In rats, cyclic depolarizations and slow waves generate myogenic contractions of low frequency (LF) and high frequency (HF), respectively. Interstitial cells of Cajal (ICC) located near the submuscular plexus (SMP) generate slow waves. Inhibitory junction potential (IJP) consists on a purinergic fast (IJPf) followed by a nitrergic slow (IJPs) component leading to relaxation. In the present study, we characterized (1) the dynamics of purinergic-nitrergic inhibitory co-transmission and (2) its contribution on prolonged inhibition of myogenic activity. Different protocols of electrical field stimulation (EFS) under different pharmacological conditions were performed to characterize electrophysiological and mechanical responses. Smooth muscle cells (SMCs) in tissue devoid of ICC-SMP had a resting membrane potential (RMP) of -40.7 ± 0.7 mV. Single pulse protocols increased purinergic and nitrergic IJP amplitude in a voltage-dependent manner (IJPfMAX = -26.4 ± 0.6 mV, IJPsMAX = -6.7 ± 0.3 mV). Trains at increasing frequencies enhanced nitrergic (k = 0.8 ± 0.2 s, IJPs∞ = -15 ± 0.5 mV) whereas they attenuated purinergic responses (k = 3.4 ± 0.6 s,IJPf∞ = -8.9 ± 0.6 mV). In tissues with intact ICC-SMP, the RMP was -50.0 ± 0.9 mV and nifedipine insensitive slow waves (10.1 ± 2.0 mV, 10.3 ± 0.5 cpm) were recorded. In these cells, (1) nitrergic and purinergic responses were reduced and (2) slow waves maintained their intrinsic frequency and increased their amplitude under nerve-mediated hyperpolarization. Based on the co-transmission process and consistent with the expected results on RMP, prolonged EFS caused a progressive reduction of LF contractions whereas HF contractions were partially insensitive. In conclusion, inhibitory neurons modulate colonic spontaneous motility and the principles determining post-junctional responses are (1) the frequency of firing that determines the neurotransmitter/receptor involved, (2) the transwall gradient and (3) the origin and nature of each myogenic activity
不同神经肌源性机制的相互作用决定了结肠的蠕动。在大鼠中，周期性去极化和慢波分别产生低频（LF）和高频（HF）的肌源性收缩。位于肌下神经丛（SMP）附近的 Cajal 间质细胞（ICC）产生慢波。抑制性接头电位（IJP）由嘌呤能快速成分（IJPf）和随后的一氧化氮能慢速成分（IJPs）组成，导致松弛。在本研究中，我们表征了（1）嘌呤能 - 一氧化氮能抑制性共传递的动力学，以及（2）其对肌源性活动长期抑制的贡献。在不同药理条件下进行不同的电场刺激（EFS）方案，以表征电生理和机械反应。缺乏 ICC - SMP 的组织中的平滑肌细胞（SMC）的静息膜电位（RMP）为 -40.7±0.7 mV。单脉冲方案以电压依赖性方式增加嘌呤能和一氧化氮能 IJP 幅度（IJPfMAX = -26.4±0.6 mV, IJPsMAX = -6.7±0.3 mV）。频率增加的串刺激增强了一氧化氮能反应（k = 0.8±0.2 s, IJPs∞ = -15±0.5 mV），而减弱了嘌呤能反应（k = 3.4±0.6 s, IJPf∞ = -8.9±0.6 mV）。在 ICC - SMP 完整的组织中，RMP 为 -50.0±0.9 mV，记录到硝苯地平不敏感的慢波（10.1±2.0 mV, 10.3±0.5 cpm）。在这些细胞中，（1）一氧化氮能和嘌呤能反应降低，（2）在神经介导的超极化下慢波保持其固有频率并增加其幅度。基于共传递过程并与 RMP 的预期结果一致，长时间的 EFS 导致 LF 收缩逐渐减少，而 HF 收缩部分不敏感。总之，抑制性神经元调节结肠的自发蠕动，决定接头后反应的原则是（1）决定所涉及的神经递质/受体的放电频率，（2）跨壁梯度，以及（3）每种肌源性活动的起源和性质
