The normal trigger for the release of acetylcholine is the arrival of a nerve action potential at the terminal. Katz and Miledi found that, if the action potential is blocked by tetrodotoxin, acetylcholine can still be released by depolarizing the terminal with applied current. However, this current is only effective when calcium ions are present in the external solution. Axon terminals contain numbers of voltage-gated calcium channels. It seems probable that these open during the action potential so that calcium ions enter the terminal and act as a trigger for the release of the contents of the vesicles.
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