Sulphonylurea receptors differently modulate ICC pacemaker Ca2+ activity and smooth muscle contractility
Sulphonylurea receptors differently modulate ICC pacemaker Ca2+ activity and smooth muscle contractility
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DOI：
10.1242/jcs.02540
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发表时间：
2005-09-15
影响因子：
4
通讯作者：
Kajioka, S
中科院分区：
文献类型：
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作者：
Nakayama, S;Ohya, S;Kajioka, S
适当的胃肠蠕动对适当控制身体能量水平至关重要。Cajal间质细胞（ICCs;用c-Kit免疫反应性鉴定）中的细胞内Ca 2+（[Ca 2 +]（i））振荡被认为是胃肠运动中起搏器活动的主要机制。在本研究中，RT-PCR检测显示磺脲类受体（SUR 1）的1型亚型在小鼠回肠ICC中的主要表达，但SUR 2的表达主要在平滑肌中。在从相同组织制备的细胞簇中，发现ICC中的平滑肌收缩性和起搏器[Ca 2 +]（i）活性受到K-ATP通道开放剂和磺酰脲类化合物的差异调节，与SUR亚型的表达一致。1 μ M cromakalim几乎完全抑制平滑肌的机械活动，而ICC起搏器[Ca 2 +]（i）振荡持续存在。更高浓度（类似于10 μ M）的cromakalim衰减起搏器[Ca 2 +]（i）振荡。这种作用不能通过改变K+的逆转电位来逆转，但可以通过格列本脲来阻止。30 μ M的二氮嗪终止了ICC起搏器[Ca 2 +]（i）振荡，但再次用高细胞外K+治疗不能恢复它们。这些结果表明，SUR可通过电压非依赖性机制调节起搏器[Ca ~（2+）]（i）振荡，并且肠起搏和血糖控制与SUR密切相关。
Appropriate gastrointestinal motility is essential to properly control the body energy level. Intracellular Ca2+ ([Ca2+](i)) oscillations in interstitial cells of Cajal (ICCs; identified with c-Kit immunoreactivity) are considered to be the primary mechanism for the pacemaker activity in gastrointestinal motility. In the present study, RT-PCR examinations revealed predominant expression of the type 1 isoform of sulphonylurea receptors (SUR1) in ICCs of the mouse ileum, but expression of SUR2 was predominant in smooth muscle. In cell clusters prepared from the same tissue, smooth muscle contractility and pacemaker [Ca2+](i) activity in ICCs were found to be differentially modulated by K-ATP channel openers and sulphonylurea compounds, in accordance with the expression of SUR isoforms. 1 mu M cromakalim nearly fully suppressed the mechanical activity in smooth muscle, whereas ICC pacemaker [Ca2+](i) oscillations persisted. Greater concentrations (similar to 10 mu M) of cromakalim attenuated pacemaker [Ca2+](i) oscillations. This effect was not reversed by changing the reversal potential of K+, but was prevented by glibenclamide. Diazoxide at 30 mu M terminated ICC pacemaker [Ca2+](i) oscillations, but again treatment with high extracellular K+ did not restore them. These results suggest that SUR can modulate pacemaker [Ca2+](i) oscillations via voltage-independent mechanism(s), and also that intestinal pacemaking and glucose control are closely associated with SUR.