A mathematical model of ENaC and Slc26a6 regulation by CFTR in salivary gland ducts.

Cystic fibrosis (CF) is a genetic disease caused by the mutations of cystic fibrosis transmembrane conductance regulator (), the cystic fibrosis transmembrane conductance regulator gene. Cftr is a critical ion channel expressed in the apical membrane of mouse salivary gland striated duct cells. Although Cftr is primarily a Cl channel, its knockout leads to higher salivary Cl and Na concentrations and lower pH.

Tools for Quantitative Analysis of Calcium Signaling Data Using Jupyter-Lab Notebooks.

Calcium signaling data analysis has become increasing complex as the size of acquired datasets increases. In this paper we present a Ca signaling data analysis method that employs custom written software scripts deployed in a collection of Jupyter-Lab "notebooks" which were designed to cope with this complexity. The notebook contents are organized to optimize data analysis workflow and efficiency.

Simulation of Calcium Dynamics in Realistic Three-Dimensional Domains.

The cytosolic concentration of free calcium ions ([Ca2+]) is an important intracellular messenger in most cell types, and the spatial distribution of [Ca2+] is often critical. In a salivary gland acinar cell, a polarised epithelial cell, whose principal function is to transport water and thus secrete saliva, [Ca2+] controls the secretion of primary saliva, but increases in [Ca2+] are localised to the apical regions of the cell. Hence, any quantitative explanation of how [Ca2+] controls saliva secretion must take into careful account the spatial distribution of the various Ca2+ sources, Ca2+ sinks, and Ca2+-sensitive ion channels.

A Mathematical Model of Salivary Gland Duct Cells.

Saliva is produced in two stages in the salivary glands: the secretion of primary saliva by the acinus and the modification of saliva composition to final saliva by the intercalated and striated ducts. In order to understand the saliva modification process, we develop a mathematical model for the salivary gland duct. The model utilises the realistic 3D structure of the duct reconstructed from an image stack of gland tissue.

Highly localized intracellular Ca signals promote optimal salivary gland fluid secretion.

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.

Calcium Dynamics and Water Transport in Salivary Acinar Cells.

Saliva is secreted from the acinar cells of the salivary glands, using mechanisms that are similar to other types of water-transporting epithelial cells. Using a combination of theoretical and experimental techniques, over the past 20 years we have continually developed and modified a quantitative model of saliva secretion, and how it is controlled by the dynamics of intracellular calcium. However, over approximately the past 5 years there have been significant developments both in our understanding of the underlying mechanisms and in the way these mechanisms should best be modelled.

A Multicellular Model of Primary Saliva Secretion in the Parotid Gland.

We construct a three-dimensional anatomically accurate multicellular model of a parotid gland acinus to investigate the influence that the topology of its lumen has on primary fluid secretion. Our model consists of seven individual cells, coupled via a common lumen and intercellular signalling. Each cell is equipped with the intracellular calcium ([Formula: see text])-signalling model developed by Pages et al, Bull Math Biol 81: 1394-1426, 2019.

A Model of [Formula: see text] Dynamics in an Accurate Reconstruction of Parotid Acinar Cells.

We have constructed a spatiotemporal model of [Formula: see text] dynamics in parotid acinar cells, based on new data about the distribution of inositol trisphophate receptors (IPR). The model is solved numerically on a mesh reconstructed from images of a cluster of parotid acinar cells. In contrast to our earlier model (Sneyd et al.

A Mathematical Model of Fluid Transport in an Accurate Reconstruction of Parotid Acinar Cells.

Salivary gland acinar cells use the calcium ([Formula: see text]) ion as a signalling messenger to regulate a diverse range of intracellular processes, including the secretion of primary saliva. Although the underlying mechanisms responsible for saliva secretion are reasonably well understood, the precise role played by spatially heterogeneous intracellular [Formula: see text] signalling in these cells remains uncertain. In this study, we use a mathematical model, based on new and unpublished experimental data from parotid acinar cells (measured in excised lobules of mouse parotid gland), to investigate how the structure of the cell and the spatio-temporal properties of [Formula: see text] signalling influence the production of primary saliva.

Modeling calcium waves in an anatomically accurate three-dimensional parotid acinar cell.

We construct a model of calcium waves in a three-dimensional anatomically accurate parotid acinar cell, constructed from experimental data. Gradients of inositol trisphosphate receptor (IPR) density are imposed, with the IPR density being greater closer to the lumen, which has a branched structure, and inositol trisphosphate (IP) is produced only at the basal membrane. We show (1) that IP equilibrates so quickly across the cell that it can be assumed to be spatially homogeneous; (2) spatial separation of the sites of IP action and IP production does not preclude the formation of stable oscillatory Ca waves.