Explicit theoretical analysis of how the rate of exocytosis depends on local control by Ca2+ channels

Hormones and neurotransmitters are released from cells by calcium-regulated exocytosis, and local coupling between Ca2+ channels (CaVs) and secretory granules is a key factor determining the exocytosis rate. Here, we devise a methodology based on Markov chain models that allows us to obtain analytic results for the expected rate. First, we analyze the property of the secretory complex obtained by coupling a single granule with one CaV. Then, we extend our results to a more general case where the granule is coupled with n CaVs. We investigate how the exocytosis rate is affected by varying the location of granules and CaVs. Moreover, we assume that the single granule can form 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 that, in case of inactivating CaVs, is more pronounced when the granule is close to CaVs, while, surprisingly, in case of non-inactivating CaV...