Spatial and temporal mapping of pacemaker activity in interstitial cells of Cajal in mouse ileum in situ
Spatial and temporal mapping of pacemaker activity in interstitial cells of Cajal in mouse ileum in situ
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DOI：
10.1152/ajpcell.00447.2005
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发表时间：
2006-05-01
影响因子：
5.5
通讯作者：
Sanders, KM
中科院分区：
文献类型：
--
作者：
Park, KJ;Hennig, GW;Sanders, KM
自发的电起搏器活动发生在胃肠道肌层，并驱动相性收缩。Cajal间质细胞(ICC)是产生和传播电慢波的起搏细胞。我们用钙离子成像技术观察了小鼠小肠肌间区(ICC-My)ICC的自发节律性。经Kit抗体标记证实，ICC-My显示电慢波后有规律的钙瞬变。ICC-My形成网络，钙瞬变波前以接近2 mm/S的速度穿过ICC-My网络，激活附着的纵行肌纤维。尼卡地平可阻断Lm的钙瞬变，但对ICC-My的瞬变无明显影响。β-甘草次酸降低了繁殖的连贯性，导致单细胞独立起搏。因此，几乎所有的ICC-My都是自发活动的，但正常的活动被组织成传播的波前。二氢吡啶抗性钙离子进入的抑制剂(Ni2+和米贝拉地尔)和升高的外部K+降低了凝聚力和繁殖速度，最终阻止了所有的活性。线粒体解偶联剂FCCP、抗菌素和肌醇1，4，5-三磷酸受体抑制药2-氨基乙氧基二苯硼酸酯可阻断ICC-My的节律性钙瞬变。这些数据表明，ICC-Mys中的全球钙瞬变是胃肠道肌肉电慢波的报告。ICC网络的成像提供了起搏器活动的独特的多细胞视角。ICC-My的活性是由细胞内钙处理机制驱动的，并受电压依赖性的钙离子内流和细胞缝隙连接耦合的影响。
Spontaneous electrical pacemaker activity occurs in tunica muscularis of the gastrointestinal tract and drives phasic contractions. Interstitial cells of Cajal (ICC) are the pacemaker cells that generate and propagate electrical slow waves. We used Ca2+ imaging to visualize spontaneous rhythmicity in ICC in the myenteric region (ICC-MY) of the murine small intestine. ICC-MY, verified by colabeling with Kit antibody, displayed regular Ca2+ transients that occurred after electrical slow waves. ICC-MY formed networks, and Ca2+ transient wave fronts propagated through the ICC-MY networks at similar to 2 mm/s and activated attached longitudinal muscle fibers. Nicardipine blocked Ca2+ transients in LM but had no visible effect on the transients in ICC-MY. beta-Glycyrrhetinic acid reduced the coherence of propagation, causing single cells to pace independently. Thus, virtually all ICC-MYs are spontaneously active, but normal activity is organized into propagating wave fronts. Inhibitors of dihydropyridine-resistant Ca2+ entry (Ni2+ and mibefradil) and elevated external K+ reduced the coherence and velocity of propagation, eventually blocking all activity. The mitochondrial uncouplers, FCCP, and antimycin and the inositol 1,4,5-trisphosphate receptor-inhibitory drug, 2-aminoethoxydiphenyl borate, abolished rhythmic Ca2(+) transients in ICC-MY. These data show that global Ca2+ transients in ICC-MYs are a reporter of electrical slow waves in gastrointestinal muscles. Imaging of ICC networks provides a unique multicellular view of pacemaker activity. The activity of ICC- MY is driven by intracellular Ca2+ handling mechanisms and entrained by voltage-dependent Ca2+ entry and coupling of cells via gap junctions.