Department of Physiology and Cell Biology, University of Nevada, Reno, School of Medicine, Reno, Nevada 89557, USA.
Department of Physiology and Cell Biology, University of Nevada, Reno, School of Medicine, Reno, Nevada 89557, USA.
Cell Calcium. 2021 Nov;99:102472. doi: 10.1016/j.ceca.2021.102472. Epub 2021 Sep 10.
Myenteric interstitial cells of Cajal (ICC-MY) generate and actively propagate electrical slow waves in the stomach. Slow wave generation and propagation are altered in gastric motor disorders, such as gastroparesis, and the mechanism for the gradient in slow wave frequency that facilitates proximal to distal propagation of slow waves and normal gastric peristalsis is poorly understood. Slow waves depend upon Ca-activated Cl channels (encoded by Ano1). We characterized Ca signaling in ICC-MY in situ using mice engineered to have cell-specific expression of GCaMP6f in ICC. Ca signaling differed in ICC-MY in corpus and antrum. Localized Ca transients were generated from multiple firing sites and were organized into Ca transient clusters (CTCs). Ca transient refractory periods occurred upon cessation of CTCs, but a relatively higher frequency of Ca transients persisted during the inter-CTC interval in corpus than in antrum ICC-MY. The onset of Ca transients after the refractory period was associated with initiation of the next CTC. Thus, CTCs were initiated at higher frequencies in corpus than in antrum ICC-MY. Initiation and propagation of CTCs (and electrical slow waves) depends upon T-type Ca channels, and durations of CTCs relied upon L-type Ca channels. The durations of CTCs mirrored the durations of slow waves. CTCs and Ca transients between CTCs resulted from release of Ca from intracellular stores and were maintained, in part, by store-operated Ca entry. Our data suggest that Ca release and activation of Ano1 channels both initiate and contribute to the plateau phase of slow waves.
Cajal 间质细胞（ICC-MY）在胃中产生并主动传播电慢波。胃动力障碍（如胃轻瘫）会改变慢波的产生和传播，而促进慢波从近端向远端传播和正常胃蠕动的慢波频率梯度的机制尚未完全了解。慢波依赖于 Ca 激活的 Cl 通道（由 Ano1 编码）。我们使用在 ICC 中特异性表达 GCaMP6f 的工程小鼠，对原位 ICC-MY 中的 Ca 信号进行了表征。胃体和胃窦 ICC-MY 中的 Ca 信号不同。局部 Ca 瞬变是从多个点火部位产生的，并组织成 Ca 瞬变簇（CTC）。在 CTC 停止后，Ca 瞬变的不应期发生，但在胃体 ICC-MY 中，与胃窦相比，在 CTC 间隔期间持续存在相对较高频率的 Ca 瞬变。在不应期后 Ca 瞬变的起始与下一个 CTC 的启动有关。因此，胃体 ICC-MY 中的 CTC 启动频率高于胃窦。CTC 的启动和传播（以及电慢波）取决于 T 型 Ca 通道，而 CTC 的持续时间取决于 L 型 Ca 通道。CTC 的持续时间反映了慢波的持续时间。CTC 和 CTC 之间的 Ca 瞬变是由于细胞内储存的 Ca 释放引起的，并部分由储存操作的 Ca 内流维持。我们的数据表明，Ca 释放和 Ano1 通道的激活都启动并有助于慢波的平台期。
