A mathematical model of intricate calcium dynamics and modulation of calcium signalling by mitochondria in pancreatic acinar cells

Neeraj Manhas and N. Anbazhagan

Chaos, Solitons & Fractals, 2021, vol. 145, issue C

Abstract: The pancreatic acinar cells display wide varieties of Ca2+ oscillations within the cell. The study of these calcium signals/oscillations are of great interest because they are physiologically important. The Ca2+ release from the endoplasmic reticulum via inositol trisphosphate receptors (IPR) and the ryanodine receptors (RyR) creates a high cytosolic Ca2+ signal in the acinar cell. The pancreatic acinar cells are highly polarized cells, and the Ca2+ response is quite extensive in the apical (peri-granular) region than the basal region of the cell. The Ca2+ signals which originated in the apical region control the exocytosis process and triggered peri-granular mitochondria (Mito) to uptake Ca2+. The peri-granular mitochondria play a critical role in confining cytosolic Ca2+ elevation by acting as a Ca2+ buffer barrier. They also participate in shaping the Ca2+ response by restricting the Ca2+ signals into the granular region of the acinar cells. They sequestered Ca2+ very rapidly. Then they release Ca2+ very slowly to provide Ca2+ supply to cause Ca2+ oscillations in the apical region. Thus, herein we proposed a Class II compartmental mathematical model which systematically simulates the complex Ca2+ oscillations in the apical region, and the peri-granular mitochondria matrix of the pancreatic acinar cells. The model assumes the functional coupling between the IPR and the RyR through the mechanism of calcium induced calcium release (CICR). In the proposed compartmental model of Ca2+ dynamics, the Ca2+ dependent production and degradations of (1,4,5) inositol-trisphosphate (IP3) along with the apical parameters, apical endoplasmic reticulum (ER), and the peri-granular mitochondria are considered. The bifurcation analysis of the model is performed which explores the intricate dynamic behaviour of the apical region of the acinar cells, and hence derive the complex Ca2+ oscillations in both the apical region and the peri-granular mitochondria. The model predicts the different patterns of Ca2+ oscillation from the regular to sinusoidal to raised-baseline to sustained spikes in the apical region of the acinar cells.

Keywords: Pancreatic Acinar Cells; Apical region; Mitochondria; Class II Model; Periodic; Sustain; Sinusoidal Spikes; Hopf; Torus; Period doubling Bifurcation (search for similar items in EconPapers)
Date: 2021
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Citations: View citations in EconPapers (1)

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Persistent link: https://EconPapers.repec.org/RePEc:eee:chsofr:v:145:y:2021:i:c:s0960077921000941

DOI: 10.1016/j.chaos.2021.110741

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