Role of Ca(2+) in the synchronization of transmitter release at calyceal synapses in the auditory system of rat.

The synchronization of transmitter release in the synapse of the medial nucleus of the trapezoid body (MNTB) is achieved during early postnatal development as a consequence of elimination of delayed asynchronous releases and appears to reflect changes in the dynamics of Ca(2+) entry and clearance. To examine the role of Ca(2+) in regulating synchronization of transmitter release in the mature synapse (after postnatal day 9, P9), we perturbed Ca(2+) dynamics systematically. Replacement of external Ca(2+) (2 mM) with Sr(2+) induced delayed asynchronous release following the major EPSC. We tried to reproduce asynchronous releases without using Sr(2+) and instead by manipulating the time course and the size of Ca(2+) transient in the presynaptic terminal, under the assumption that replacement of external Na(+) with Li(+) or application of eosin-Y would prolong the lifetime of Ca(2+) transient by reducing the rate of Ca(2+) extrusion from the terminal. With application of Li(+), Ca(2+) transient in the terminal was prolonged, the EPSC decay time course was prolonged, and the EPSC amplitude increased. However, these EPSCs were not followed by delayed asynchronous release. When Ca(2+) influx was reduced, either by partial Ca(2+) channel blockade with a low concentration of Cd(2+) or omega-agatoxin IVA, a marked asynchronous release resulted. This was further enhanced by the combined application of Li(+) or eosin-Y. These results suggest that cooperative increases of both Ca(2+) influx and Ca(2+) clearance capacities leading to a sharper Ca(2+) spike in the presynaptic terminal underlie synchronized transmitter release in the presynaptic terminal of the MNTB.