Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.
J Physiol. 2011 Dec 15;589(Pt 24):6105-18. doi: 10.1113/jphysiol.2011.217497. Epub 2011 Oct 17.
Extracellular electrical recording and studies using animal models have helped establish important concepts of human gastric physiology. Accepted standards include electrical quiescence in the fundus, 3 cycles per minute (cpm) pacemaker activity in corpus and antrum, and a proximal-to-distal slow wave frequency gradient. We investigated slow wave pacemaker activity, contractions and distribution of interstitial cells of Cajal (ICC) in human gastric muscles. Muscles were obtained from patients undergoing gastric resection for cancer, and the anatomical locations of each specimen were mapped by the operating surgeon to 16 standardized regions of the stomach. Electrical slow waves were recorded with intracellular microelectrodes and contractions were recorded by isometric force techniques. Slow waves were routinely recorded from gastric fundus muscles. These events had similar waveforms as slow waves in more distal regions and were coupled to phasic contractions. Gastric slow wave frequency was significantly greater than 3 cpm in all regions of the stomach. Antral slow wave frequency often exceeded the highest frequency of pacemaker activity in the corpus. Chronotropic mechanisms such as muscarinic and prostaglandin receptor binding, stretch, extracelluar Ca(2+) and temperature were unable to explain the observed slow wave frequency that exceeded accepted normal levels. Muscles from all regions through the thickness of the muscularis demonstrated intrinsic pacemaker activity, and this corresponded with the widespread distribution in ICC we mapped throughout the tunica muscularis. Our findings suggest that extracellular electrical recording has underestimated human slow wave frequency and mechanisms of human gastric function may differ from standard laboratory animal models.
细胞外电记录和动物模型研究有助于建立人类胃生理学的重要概念。公认的标准包括胃底的电静止、体部和胃窦每分钟 3 个周期(cpm)的起搏活动以及从近端到远端的慢波频率梯度。我们研究了人类胃肌中的慢波起搏活动、收缩和 Cajal 间质细胞(ICC)的分布。肌肉取自因癌症而行胃切除术的患者,手术医生将每个标本的解剖位置映射到胃的 16 个标准区域。通过细胞内微电极记录慢波,通过等长力技术记录收缩。从胃底肌肉常规记录慢波。这些事件具有与更远端区域的慢波相似的波形,并与相伴随的收缩偶联。胃的慢波频率在胃的所有区域均显著大于 3 cpm。胃窦的慢波频率通常超过体部起搏活动的最高频率。拟胆碱能和前列腺素受体结合、拉伸、细胞外 Ca(2+)和温度等变时机制无法解释观察到的超过可接受正常水平的慢波频率。从肌肉层的所有区域穿过肌层都表现出固有起搏活动,这与我们在整个肌层中映射到的 ICC 的广泛分布相对应。我们的发现表明,细胞外电记录低估了人类慢波频率,人类胃功能的机制可能与标准的实验室动物模型不同。