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 Ca2+ 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 Ca2+ signals and salivary secretion in live mice expressing GCamp6F, following stimulation of the nerves innervating the submandibular gland. Consistent with in vitro studies, Ca2+ signals were initiated in the apical endoplasmic reticulum. In marked contrast to in vitro data, highly localized trains of Ca2+ 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 Ca2+ signals.
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2,3,4,5,6,9,10,11
- David I Yule
- David I Yule
- James Sneyd
- Amanda Wahl
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All animal procedures were approved by University Committee on Animal Resources (UCAR-2001-214E)
- Richard S Lewis, Stanford University School of Medicine, United States
- Received: December 31, 2020
- Accepted: July 8, 2021
- Accepted Manuscript published: July 9, 2021 (version 1)
© 2021, Takano et al.
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