Presynaptic terminal acetylcholine receptors are located at or near nerve terminal and modulate the release of neurotransmitter such as glutamate, noradrenaline and dopamine. Activation of presynaptic acetylcholine receptors leads to influx of Ca2+ and sufficient increase in local Ca2+ concentrations which could be due to either direct or indirect Ca2+ entry. Direct Ca2+ entry through acetylcholine receptors containing alpha3 beta4 receptors is sufficient for the release of noradrenaline in hippocampus. Indirect Ca2+ increase could be due to Na+ dependent depolarization and activation of voltage dependent calcium channels (VDCC) as in the case of dopamine release. Local Ca2+ increase could also be due to an initial Ca2+ influx through acetlycholine homomeric receptors containing alpha7 subunits and further increase in Ca2+ is elicited due to Ca2+ induced Ca2+ release (CICR) that involves the ryanodine receptors in the ER and the IP3 receptors. This mechanism is used in hippocampal mossyfibre pathway. Nicotinic acetylcholine receptors may permit both sodium and calcium ions, however, the ratio of sodium and calcium influx makes these receptors either highly sodium permeable or highly calcium permeable.