Diversity and Similarity of Pacemakers in Peripheral Autonomic Nervous System

最近有研究表明，不仅是心脏，起搏器细胞在产生含有平滑肌的组织和器官（如胃肠道、膀胱、淋巴管等）的自发节律性方面也起着重要作用，自主神经系统组织了它们的活动。在研究资助期间（2003.4-2006.3），我们研究了自发节律的机制。首先，我们揭示了细胞内Ca^<2+>释放通道的协同作用，如ryanodine受体（RyR）和InsP_3受体（InsP_3R），产生起搏器[Ca^<2+>]_i振荡，支持Ca^<2+>从细胞外空间内流[可能是由于瞬时受体电位样（TRP）非选择性阳离子通道]。特别是，我们的研究首次提供了RyR参与胃、小肠和由胚胎干细胞形成的肠样器官的起搏器[Ca^<2+>]_i振荡的证据。最近，韩国的一个研究小组报道了melastatin型TRP通道7 （TRPM7）在ICC起搏中起重要作用。有趣的是，这种非选择性阳离子通道可能对应于我们用核磁共振证明的Na^+无关的Mg^<2+>内流。我们的实验还表明，与胰型磺酰脲受体相关的特殊嘌呤受体（P2X_2和P2X_5）和ATP敏感的K通道（K_<ATP>）对ICC起搏器[Ca^<2+>]_i振荡具有重要的调节作用。此外，我们发现胃肠道间质瘤细胞中保留了一些起搏器[Ca^<2+1>]i振荡所必需的离子通道。最后，我想提一下关于逼尿肌平滑肌细胞的实验。逼尿肌细胞在毒蕈碱受体刺激时显示自发电流。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的帮助。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