Calcium binding sites of the transmitter release mechanism: clues from short-term facilitation

The binding of multiple, probably four, calcium ions to an intraterminal protein is believed to be an integral step in the gating of neurotransmitter release. We have reexamined the clues to this ion-protein interaction inferred from experimental results on transmitter release and its facilitation. It is argued that while one of the four calcium binding sites required to activate transmitter release may have a relatively low affinity, results obtained from studies on short-term facilitation suggest that the other sites have affinities that range from intermediate to relatively high. A low calcium affinity should not, therefore, be regarded as obligatory requirement in the identification of the calcium binding protein.