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Open AccessArticle

From Local to Global Modeling for Characterizing Calcium Dynamics and Their Effects on Electrical Activity and Exocytosis in Excitable Cells

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Department of Information Engineering, University of Padova, 35131 Padova, Italy
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Department of Mathematics “Tullio Levi-Civita”, University of Padova, 35131 Padova, Italy
3
Padova Neuroscience Center, University of Padova, 35131 Padova, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(23), 6057; https://doi.org/10.3390/ijms20236057
Received: 4 September 2019 / Revised: 27 November 2019 / Accepted: 27 November 2019 / Published: 30 November 2019
(This article belongs to the Special Issue Calcium Signaling in Human Health and Diseases 2.0)
Electrical activity in neurons and other excitable cells is a result of complex interactions between the system of ion channels, involving both global coupling (e.g., via voltage or bulk cytosolic Ca2+ concentration) of the channels, and local coupling in ion channel complexes (e.g., via local Ca2+ concentration surrounding Ca2+ channels (CaVs), the so-called Ca2+ nanodomains). We recently devised a model of large-conductance BKCa potassium currents, and hence BKCa–CaV complexes controlled locally by CaVs via Ca2+ nanodomains. We showed how different CaV types and BKCa–CaV stoichiometries affect whole-cell electrical behavior. Ca2+ nanodomains are also important for triggering exocytosis of hormone-containing granules, and in this regard, we implemented a strategy to characterize the local interactions between granules and CaVs. In this study, we coupled electrical and exocytosis models respecting the local effects via Ca2+ nanodomains. By simulating scenarios with BKCa–CaV complexes with different stoichiometries in pituitary cells, we achieved two main electrophysiological responses (continuous spiking or bursting) and investigated their effects on the downstream exocytosis process. By varying the number and distance of CaVs coupled with the granules, we found that bursting promotes exocytosis with faster rates than spiking. However, by normalizing to Ca2+ influx, we found that bursting is only slightly more efficient than spiking when CaVs are far away from granules, whereas no difference in efficiency between bursting and spiking is observed with close granule-CaV coupling. View Full-Text
Keywords: mathematical modeling; Ca2+ dynamics; ion channel complex; electrical activity; exocytosis mathematical modeling; Ca2+ dynamics; ion channel complex; electrical activity; exocytosis
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MDPI and ACS Style

Montefusco, F.; Pedersen, M.G. From Local to Global Modeling for Characterizing Calcium Dynamics and Their Effects on Electrical Activity and Exocytosis in Excitable Cells. Int. J. Mol. Sci. 2019, 20, 6057.

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