Diversity and Similarity of Pacemakers in Peripheral Autonomic Nervous System

最近有人提出，不仅心脏，起搏细胞在产生含有平滑肌的组织和器官[例如胃肠道（GI）、膀胱、淋巴管等]的自发节律性中起重要作用，自主神经系统负责组织它们的活动。在研究补助金的任期内（2003.4-2006.3），我们研究了自发节律性的机制，首先，我们揭示了细胞内Ca^2+释放通道，如Ryanodine受体（RyR）和InsP_3受体（InsP_3R）的协同作用，产生起搏[Ca^2+]_i振荡，支持来自细胞外间隙的Ca^2+内流[推测是由于瞬时受体电位样（TRP）非选择性阳离子通道]。特别是，我们的研究首次为RyR参与胃、小肠和胚胎干形成的肠样器官的起搏[Ca^<2+>]_i振荡提供了证据（ 关于我们 最近，韩国的一个研究小组报道了Melastatin型TRP通道7（TRPM 7）在ICC起搏中起着重要作用。有趣的是，这种非选择性阳离子通道可能与我们用核磁共振证实的Na^+非依赖性Mg^2+内流相对应，我们的实验还表明，与胰腺型磺酰脲受体相关的特殊嘌呤受体（P2X_2和P2X_5）和ATP敏感性K通道（K_<ATP>）对ICC起搏点[Ca^2+]_i振荡起重要调节作用。此外，我们还发现GIST（gastrointestinal stromal tumuor）细胞中保存了一些对[Ca^（2+1）]i起起搏作用的离子通道。逼尿肌细胞在毒蕈碱受体刺激期间显示自发电流。实际上，这种自发活动的结果对计划研究ICC起搏器活动的实验有很大帮助。少

It has recently been suggested that not only the heart, pacemaker cells play an important role in generating spontaneous rhythmicity of the tissues and organs containing smooth muscle [e.g. gastrointestinal (GI) tracts, urinary bladder, lymph ducts, etc.], and that autonomic nervous system organizes their activity. During the tenure of the research grant (2003.4-2006.3), we investigated mechanisms underlying the spontaneous rhythmicity.First, we have revealed that revealed that co-ordinate actions of intracellular Ca^<2+> release channels, such as ryanodine receptors (RyR) and InsP_3 receptors (InsP_3R), yield pacemaker [Ca^<2+>]_i oscillations, in support with Ca^<2+> influx from the extracellular space [presumably due to transient receptor potential-like (TRP) non-selective cation channels]. Especially, our study has provided the first evidence for the involvement of RyR in pacemaker [Ca^<2+>]_i oscillations of stomach, small intestine, and gut-like organ formed from embryonic stem ( … More ES) cells.Very recently, a Korean group has reported that Melastatin-type TRP channel 7 (TRPM7) plays an essental role in ICC pacemaking. Interestingly, this non-selective cation channel presumably corresponds to Na^+ -independent Mg^<2+> influx that we had demonstrated using nuclear magnetic resonance.Our experiments also have suggested that special purinoceptors (P2X_2 and P2X_5) and ATP-sensitive K channels (K_<ATP>) associated with pancreatic-type sulphonylurea receptors provide important modulation on ICC pacemaker [Ca^<2+>]_i oscillations. Furthermore, we have revealed that some ion channels essential for pacemaker [Ca^<2+1>]i oscillations are preserved in GIST (gastrointestinal stromal tumuor) cells.Lastly, I would like to mention about experiments in detrusor smooth muscle cells. Detrusor cells show spontaneous electrical currents during muscarinic receptor stimulation. Actually, the results on this spontaneous activity have greatly helped in planning experiments to investigate ICC pacemaker activity. Less