A mathematical study of the role of calcium in the regulation of saliva secretion

Xerostomia is estimated to affect 30% of adults over the age of 65. The condition is characterised by a lack of saliva secretion, resulting in a range of health problems. A rise in the concentration of free cytosolic calcium (Ca²⁺) is essential to initiate saliva secretion. We construct mathematical models of saliva secretion and Ca²⁺ dynamics in salivary acinar and duct cells. We investigate how the distribution of K⁺ channels affects the rate of primary saliva secretion. Maximum saliva secretion is hypothesised to occur when a small amount of K⁺ conductance is located in the apical membrane, with the majority in the basolateral membrane. Apical K⁺ channels have since been experimentally located. For a range of applied agonist, the concentration of Ca²⁺ in salivary cells is seen experimentally to oscillate and to travel in waves across the cytosol. We construct a model of Ca2+ oscillations in parotid acinar cells that requires paired oscillations of IP₃. This ODE model reproduces a number of experimentally observed phenomena. The model is later spatially extended. An inhomogeneous distribution of Ca²⁺ channels is shown to produce apical to basal Ca²⁺ waves, as seen experimentally. We investigate how Ca²⁺ wave properties affect the rate of saliva secretion. Mean Ca²⁺ concentration is found to be the most significant property in regulating secretion. Wave speed was found to encode a range of secretion rates. Ca²⁺ oscillation frequency and amplitude had little effect on the fluid secretion rate. Recent experimental results show coupled oscillations of Ca²⁺ and IP3 in HSY cells, a duct cell line. We present a mathematical model of HSY cells in which IP₃ oscillations are not required for the generation of Ca²⁺ oscillations. The inclusion of passive IP₃ oscillations is shown to increase the Ca²⁺ oscillation frequency range and be consistent with the experimental data. These single-cell models provide insight into the regulation of saliva secretion by themselves. They also suggest what is important to include, and what can be simplified in constructing a whole-organ model. With a greater understanding of the regulation of saliva secretion, and the role Ca²⁺ plays, it is hoped that we might learn how salivary gland dysfunction occurs.

Name thesis:degree_name

PhD

Level thesis:degree_level

Doctoral

Grantor dc:publisher

ResearchSpace@Auckland

Year dc:date.issued

2012

Author dc:creator

• Palk, Laurence

Advisors dc:contributor.advisor

• Sneyd, J
• Crampin, E

Statement dc:rights

• Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.

Licence dc:rights.uri

• https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm

Handle dc:identifier.uri

https://hdl.handle.net/2292/20068

OAI identifier oai:identifier

oai:researchspace.auckland.ac.nz:2292/20068