The 'Ca-voltage' hypothesis for neurotransmitter release

The 'Ca-voltage' hypothesis for neurotransmitter release was reinvestigated by studying the kinetics of neurotransmitter release. These were independent of changes in intracellular or extracellular Ca2+ concentration. It is concluded that initiation and termination of release do not result from rapid entry and removal of Ca2+ although Ca2+ is essential for release. Quantal release of transmitter requires depolarization-dependent transformation of a membrane molecule from an inactive form T to a Ca2+-binding form S. The depolarization-dependent T----S transformation initiates release in the presence of Ca2+. The S----T transformation upon repolarization stops release even though the Ca2+ concentration at release sites is still high.