Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Belfast, Northern Ireland, United Kingdom.
PLoS One. 2013;8(1):e53423. doi: 10.1371/journal.pone.0053423. Epub 2013 Jan 9.
Several populations of interstitial cells of Cajal (ICC) exist in the bladder, associated with intramural nerves. Although ICC respond to exogenous agonists, there is currently no evidence of their functional innervation. The objective was to determine whether bladder ICC are functionally innervated. Guinea-pig bladder tissues, loaded with fluo-4AM were imaged with fluorescent microscopy and challenged with neurogenic electrical field stimulation (EFS). All subtypes of ICC and smooth muscle cells (SMC) displayed spontaneous Ca(2+)-oscillations. EFS (0.5 Hz, 2 Hz, 10 Hz) evoked tetrodotoxin (1 µM)-sensitive Ca(2+)-transients in lamina propria ICC (ICC-LP), detrusor ICC and perivascular ICC (PICC) associated with mucosal microvessels. EFS responses in ICC-LP were significantly reduced by atropine or suramin. SMC and vascular SMC (VSM) also responded to EFS. Spontaneous Ca(2+)-oscillations in individual ICC-LP within networks occurred asynchronously whereas EFS evoked coordinated Ca(2+)-transients in all ICC-LP within a field of view. Non-correlated Ca(2+)-oscillations in detrusor ICC and adjacent SMC pre-EFS, contrasted with simultaneous neurogenic Ca(2+) transients evoked by EFS. Spontaneous Ca(2+)-oscillations in PICC were little affected by EFS, whereas large Ca(2+)-transients were evoked in pre-EFS quiescent PICC. EFS also increased the frequency of VSM Ca(2+)-oscillations. In conclusion, ICC-LP, detrusor ICC and PICC are functionally innervated. Interestingly, Ca(2+)-activity within ICC-LP networks and between detrusor ICC and their adjacent SMC were synchronous under neural control. VSM and PICC Ca(2+)-activity was regulated by bladder nerves. These novel findings demonstrate functional neural control of bladder ICC. Similar studies should now be carried out on neurogenic bladder to elucidate the contribution of impaired nerve-ICC communication to bladder pathophysiology.
几种 Cajal 间质细胞（ICC）存在于与壁内神经相关的膀胱中。尽管 ICC 对外源性激动剂有反应，但目前尚无其功能性神经支配的证据。目的是确定膀胱 ICC 是否具有功能性神经支配。用荧光显微镜对加载 fluo-4AM 的豚鼠膀胱组织进行成像，并进行神经源性电刺激（EFS）。所有 ICC 亚型和平滑肌细胞（SMC）均显示自发的 Ca（2+）振荡。EFS（0.5 Hz、2 Hz、10 Hz）在黏膜微血管相关的固有层 ICC（ICC-LP）、逼尿肌 ICC 和血管周围 ICC（PICC）中引起河豚毒素（1 μM）敏感的 Ca（2+）瞬变。ICC-LP 中的 EFS 反应被阿托品或苏拉明显著降低。SMC 和血管平滑肌（VSM）也对 EFS 有反应。网络中单个 ICC-LP 中的自发 Ca（2+）振荡异步发生，而 EFS 则在视野内的所有 ICC-LP 中引起协调的 Ca（2+）瞬变。EFS 前，ICC-LP 中的非相关 Ca（2+）振荡与 EFS 诱发的同时性神经源性 Ca（2+）瞬变形成对比。PICC 中的自发 Ca（2+）振荡受 EFS 影响较小，而在 EFS 前静止的 PICC 中则引起大的 Ca（2+）瞬变。EFS 还增加了 VSM Ca（2+）振荡的频率。总之，ICC-LP、逼尿肌 ICC 和 PICC 具有功能性神经支配。有趣的是，在神经控制下，ICC-LP 网络内和逼尿肌 ICC 与其相邻 SMC 之间的 Ca（2+）活性是同步的。VSM 和 PICC Ca（2+）活性受膀胱神经调节。这些新发现表明膀胱 ICC 具有功能性神经控制。现在应该对神经源性膀胱进行类似的研究，以阐明受损的神经-ICC 通讯对膀胱病理生理学的贡献。
