Dataset Information

EGTA Can Inhibit Vesicular Release in the Nanodomain of Single Ca2+ Channels.

ABSTRACT: 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 reduction in the Ca2+ concentration by EGTA is masked. By contrast, when the sensor is in a linear range, even a small reduction in Ca2+ by EGTA can decrease vesicular release. In proximity to a channel, the vesicular sensor is often saturated for a long voltage step, but not for a brief Ca2+ influx typically evoked by an action potential. Therefore, when EGTA is used as a diagnostic tool to probe the coupling distance, care must be taken regarding the presynaptic Ca2+ entry duration as well as the property of the vesicular Ca2+ sensor.

SUBMITTER: Nakamura Y

PROVIDER: S-EPMC6779814 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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EGTA Can Inhibit Vesicular Release in the Nanodomain of Single Ca2+ Channels.

Nakamura Yukihiro Y

Frontiers in Synaptic Neuroscience 20191001

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+ ...[more]

PMID: 31632263

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EGTA Can Inhibit Vesicular Release in the Nanodomain of Single Ca2+ Channels.

Publications

EGTA Can Inhibit Vesicular Release in the Nanodomain of Single Ca<sup>2+</sup> Channels.

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