biostudies-literatureUnknown11Nakamura YJapan Science and Technology AgencyThe exogenous Ca2+ chelator EGTA (ethylene glycol tetraacetic acid) has been widely used to probe the coupling distance between Ca2+ channels and vesicular Ca2+ sensors for neurotransmitter release. Because of its slow forward rate for binding, EGTA is thought to not capture calcium ions in very proximity to a channel, whereas it does capture calcium ions at the remote distance. However, in this study, our reaction diffusion simulations (RDSs) of Ca2+ combined with a release calculation using vesicular sensor models indicate that a high concentration of EGTA decreases Ca2+ and vesicular release in the nanodomain of single channels. We found that a key determinant of the effect of EGTA on neurotransmitter release is the saturation of the vesicular sensor. When the sensor is saturated, the rFrontiers in synaptic neuroscience26https://www.ebi.ac.uk/biostudies/studies/S-EPMC6779814biostudies-literatureEGTA Can Inhibit Vesicular Release in the Nanodomain of Single Ca2+ Channels.PMC6779814Nakamura YfalseEGTA Can Inhibit Vesicular Release in the Nanodomain of Single Ca2+ Channels.The exogenous Ca2+ chelator EGTA (ethylene glycol tetraacetic acid) has been widely used to probe the coupling distance between Ca2+ channels and vesicular Ca2+ sensors for neurotransmitter release. Because of its slow forward rate for binding, EGTA is thought to not capture calcium ions in very proximity to a channel, whereas it does capture calcium ions at the remote distance. However, in this study, our reaction diffusion simulations (RDSs) of Ca2+ combined with a release calculation using vesicular sensor models indicate that a high concentration of EGTA decreases Ca2+ and vesicular release in the nanodomain of single channels. We found that a key determinant of the effect of EGTA on neurotransmitter release is the saturation of the vesicular sensor. When the sensor is saturated, the r2019-01-01T00:00:00Z20192025-04-18T17:11:06.643Z2019-10-30T08:17:53ZS-EPMC67798143163226310.3389/fnsyn.2019.00026