Liu L W, Thuneberg L, Huizinga J D
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Dev Dyn. 1998 Nov;213(3):271-82. doi: 10.1002/(SICI)1097-0177(199811)213:3<271::AID-AJA4>3.0.CO;2-R.
Intestinal motor patterns are not well developed in premature infants. Similarly, in neonatal mice, irregular motor patterns were observed. Pacemaker cells, identified in the small intestine as interstitial cells of Cajal (ICCs) associated with Auerbach's plexus (ICC-APs), contribute to the generation of peristaltic movements. The objective of the present study was to assess the hypothesis that abnormal gut motor activity in (preterm) newborns can be associated with underdeveloped ICCs. Specifically, the aim was to identify at which point the electrical pacemaker activity is fully developed and whether or not the development of pacemaker activity has a structural correlation with the developmental stage of ICCs. Pacemaker activity was identified as that component of the slow wave that is insensitive to L-type calcium (Ca2+) channel blockers and displays a characteristic reduction in frequency in the presence of cyclopiazonic acid (CPA), a specific inhibitor of the endoplasmic reticulum Ca2+ pump. In newborn, unfed neonates, action potentials occurred that were irregular in frequency and amplitude and sensitive to verapamil. CPA (5 microM) abolished all action potentials. Quiescent spots were observed in approximately 50% of impalements. Six hours after birth, slow-wave activity appeared at a regular frequency and amplitude, and a well-defined plateau phase was observed. Verapamil did not affect the frequency, 5 microM CPA decreased it. The effect of CPA on the pacemaker frequency 2 days after birth was identical to that observed in adult mice. In 2-hr-old neonates, ICCs could be identified through selective uptake of methylene blue, but ultrastructural features were not fully developed. At 48 hr, a complete ICC network covering Auerbach's plexus was formed, confirmed by electron microscopy. In summary, the pacemaker component of the slow waves can be identified in neonates as early as 6 hr after birth. The pacemaker component was fully developed 2 days after birth. These electrophysiological observations correlated with the development of full network characteristics of ICC-APs and the development of fully differentiated ICC-APs from "blast-like" cells.
早产儿的肠道运动模式发育不完善。同样，在新生小鼠中也观察到不规则的运动模式。在小肠中被鉴定为与奥尔巴赫神经丛相关的 Cajal 间质细胞（ICC-APs）的起搏细胞，有助于蠕动运动的产生。本研究的目的是评估以下假设：（早产）新生儿肠道运动活动异常可能与 ICCs 发育不全有关。具体而言，目的是确定电起搏活动在何时完全发育，以及起搏活动的发育是否与 ICCs 的发育阶段存在结构相关性。起搏活动被确定为慢波的那个成分，它对 L 型钙（Ca2+）通道阻滞剂不敏感，并且在存在内质网 Ca2+泵的特异性抑制剂环匹阿尼酸（CPA）时显示出特征性的频率降低。在新生的、未喂食的新生儿中，出现了频率和幅度不规则且对维拉帕米敏感的动作电位。CPA（5 microM）消除了所有动作电位。在大约 50%的刺入点观察到静止点。出生后 6 小时，出现了频率和幅度规律的慢波活动，并观察到一个明确的平台期。维拉帕米不影响频率，5 microM CPA 使其降低。出生后 2 天 CPA 对起搏频率的影响与在成年小鼠中观察到的相同。在 2 小时大的新生儿中，可以通过亚甲蓝的选择性摄取来识别 ICCs，但超微结构特征尚未完全发育。在 48 小时时，通过电子显微镜证实形成了覆盖奥尔巴赫神经丛的完整 ICC 网络。总之，慢波的起搏成分在新生儿出生后 6 小时即可识别。起搏成分在出生后 2 天完全发育。这些电生理观察结果与 ICC-APs 的完整网络特征的发育以及从“胚样”细胞发育而来的完全分化的 ICC-APs 相关。
