Two components of transmitter release at a central synapse.

After the arrival of a presynaptic nerve impulse at an excitatory synapse in hippocampal neurons, the rate of neurotransmitter release increases rapidly and then returns to low levels with a biphasic decay. The two kinetically distinct components are differentially affected when Sr2+ is substituted for Ca2+ ions. Our findings are comparable to those of the classical studies for the frog neuromuscular junction, and thus the basic aspects of Ca(2+)-activated transmitter release machinery appear to be conserved in central synapses. The method we have used, in addition, permits us to estimate the average neurotransmitter release rate for a single bouton. The observation of differential Ca2+/Sr2+ sensitivity is consistent with a release mechanism mediated by two Ca2+ sensors with distinct Ca2+ affinities: the low-affinity Ca2+ sensor facilitates the fast synchronous phase of release, whereas the high-affinity sensor sustains the slow asynchronous phase of release.