Biophysical Society Thematic Meeting| Padova 2019

Quantitative Aspects of Membrane Fusion and Fission

Friday Speaker Abstracts

HOW IS GRANULE RELEASE AFFECTED BY LOCATION AND NUMBER OF DIFFERENT TYPES OF CA 2+ CHANNELS? MARKOV CHAIN MODELS PROVIDE ANALYTIC RESULTS Francesco Montefusco 1 ; Morten G Pedersen 1,2,3 ; 1 University of Padova, Department of Information Engineering, Padova, Italy 2 University of Padova, Department of Mathematics "Tullio Levi-Civita", Padova, Italy 3 University of Padova, Padova Neuroscience Center, Padova, Italy Most endocrine cells release hormones by calcium-regulated exocytosis: in response to a series of cellular mechanisms culminating with an increase in the intracellular Ca 2+ levels, secretory granules fuse with the cell membrane and release hormones.Here, we devise a methodology in order to characterize the local interactions between granules and Ca 2+ channels (CaVs), by developing Markov chain models that allow us to obtain analytic results for the expected exocytosis rate.First, we analyze the property of the secretory complex obtained by coupling a single granule with one CaV and, then, we extend our results to a more general case with n CaVs. We show that the distance of granule from CaVs is a major factor in determining the exocytosis rate, as recently demonstrated. Moreover, we assume that the granule forms complexes with inactivating or non-inactivating CaVs. We find that increasing the number of CaVs coupled with the granule determines a much higher rise of the exocytosis rate, which in the case of inactivating CaVs is more pronounced when the granule is close to CaVs (about 10 nm), whereas for non-inactivating CaVs the highest relative increase in rate is obtained when the granule is far from CaVs (about 50 nm), suggesting that it is not necessary that the granule is very close to CaVs for triggering exocytosis.Finally, we study the relationship between calcium influx and exocytosis and find that the quantities are typically linearly related, as experimentally observed. For the case of inactivating CaVs, our analysis shows a change of the linear relation due to near-complete inactivation of CaVs: during inactivation, the effective number of CaVs reduces and hence the relation slope decreases. This confirms that a concave relation between exocytosis and calcium influx does not necessarily reflect granule pool depletion and provides a new example of such a scenario.

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