Spatio-Temporal Calcium Dynamics of the Interstitial Cells of Cajal

The Interstitial Cells of Cajal (ICC) are responsible for producing pacemaking signals that stimulate rhythmic contractions in the gastro-intestinal system. The pacemaking signals are generated by membrane depolarizations, which are in turn linked to the integrated transport of calcium between the endoplasmic reticulum (ER), through inositol-trisphosphate receptor (IP3R) release, and mitochondria, through the uniporter. In the intestinal regions, a non-specific cation channel (NSCC) is associated with the membrane depolarizations, and is inhibited by intracellular calcium. One theory proposes that the integrated calcium transport occurs within specific regions of the ICC called "pacemaker units", and results in localized calcium concentration reductions within these units, which in turn activate the NSCC and depolarize the membrane. We have constructed a model of the spatiotemporal calcium dynamics within an ICC pacemaker unit to determine under what conditions the local calcium concentrations may reduce below baseline. We obtain reductions of calcium concentrations below baseline but only under certain conditions. Without strong and persistent stimulation of the IP3R, reductions of calcium below baseline occur only with a nonphysiological, time-dependent uniporter. Alternatively, sufficient IP3R release leads to reductions of calcium below baseline, due to depletion of the ER calcium store over the timescale of seconds, although these reductions require strong mitochondrial and ER calcium uptake.

Name thesis:degree_name

PhD

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Applied Mathematics

Grantor dc:publisher

ResearchSpace@Auckland

Year dc:date.issued

2010

Author dc:creator

• Means, Shawn

Advisor dc:contributor.advisor

• Sneyd, J

Statement dc:rights

• Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Licence dc:rights.uri

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

Handle dc:identifier.uri

https://hdl.handle.net/2292/6117

OAI identifier oai:identifier

oai:researchspace.auckland.ac.nz:2292/6117