The characteristics of intracellular Ca²⁺signalsin vivonecessitate a new model for salivary fluid secretion

Abstract

Salivary fluid secretion involves an intricate choreography to result in the trans-epithelial movement of NaCl and water into the acinus lumen. Current models are 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. 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 propagate from the apical region were observed. Following stimuli optimum for secretion, large apical-basal gradients were elicited. Given this incompatibility to the previous model, a new mathematical model was constructed to explain how salivary secretion can be efficiently stimulated by apically localized Ca2+ signals.

Optimizing Soluble Cues for Salivary Gland Tissue Mimetics Using a Design of Experiments (DoE) Approach

“…Carbachol (CCh), a muscarinic agonist, and ATP, a purinergic agonist, both stimulate intracellular calcium flux. CCh helps drive fluid secretion, and increased response to CCh correlates with increased saliva production [ 48 ]. On the other hand, excessive purinergic signaling can be an indicator of cell stress or damage [ 49 ].…”