Department of Pharmacology and Physiology, University of Rochester, Rochester, United States.
Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fujisawa, Japan.
Elife. 2021 Jul 9;10:e66170. doi: 10.7554/eLife.66170.
Salivary fluid secretion involves an intricate choreography of membrane transporters to result in the trans-epithelial movement of NaCl and water into the acinus lumen. Current models are largely based on experimental observations in enzymatically isolated cells where the Ca signal invariably propagates globally and thus appears ideally suited to activate spatially separated Cl and K channels, present on the apical and basolateral plasma membrane, respectively. We monitored Ca signals and salivary secretion in live mice expressing GCamp6F, following stimulation of the nerves innervating the submandibular gland. Consistent with in vitro studies, Ca signals were initiated in the apical endoplasmic reticulum. In marked contrast to in vitro data, highly localized trains of Ca transients that failed to fully propagate from the apical region were observed. Following stimuli optimum for secretion, large apical-basal gradients were elicited. A new mathematical model, incorporating these data was constructed to probe how salivary secretion can be optimally stimulated by apical Ca signals.
唾液分泌涉及膜转运蛋白的复杂协同作用，导致 NaCl 和水经跨上皮运动进入腺泡腔。目前的模型主要基于酶解分离细胞的实验观察，其中 Ca 信号总是全局性传播，因此似乎非常适合激活分别位于顶端和基底外侧质膜上的空间分离的 Cl 和 K 通道。我们在表达 GCamp6F 的活体小鼠中监测 Ca 信号和唾液分泌，刺激支配颌下腺的神经。与体外研究一致，Ca 信号在顶端内质网中起始。与体外数据形成鲜明对比的是，观察到未能从顶端区域充分传播的高度局部化的 Ca 瞬变串。在最适合分泌的刺激下，会引发大的顶端-基底梯度。构建了一个新的数学模型，纳入这些数据以探究顶端 Ca 信号如何最佳刺激唾液分泌。
