Abstract
A puzzling property of synaptic transmission, originally established at the neuromuscular junction, is that the time course of transmitter release is independent of the extracellular Ca(2+) concentration ([Ca(2+)]o), whereas the rate of release is highly [Ca(2+)]o-dependent. Here, we examine the time course of release at inhibitory basket cell-Purkinje cell synapses and show that it is independent of [Ca(2+)]o. Modeling of Ca(2+)-dependent transmitter release suggests that the invariant time course of release critically depends on tight coupling between Ca(2+) channels and release sensors. Experiments with exogenous Ca(2+) chelators reveal that channel-sensor coupling at basket cell-Purkinje cell synapses is very tight, with a mean distance of 10-20 nm. Thus, tight channel-sensor coupling provides a mechanistic explanation for the apparent [Ca(2+)]o independence of the time course of release.
Highlights
Calcium plays a key role in the control of transmitter release at chemical synapses (Neher, 1998; Südhof, 2013)
In contrast to this expectation, the time course of release (TCR) at the neuromuscular junction is independent of the extracellular Ca2+ concentration ([Ca2+]o) (Datyner and Gage, 1980; Van der Kloot, 1988; Parnas et al, 1989)
Action potentials were evoked in the presynaptic basket cells (BCs) in whole-cell current-clamp or cell-attached voltage-clamp configurations, whereas IPSCs were recorded in the postsynaptic Purkinje cells (PCs) under whole-cell voltage-clamp conditions
Summary
Calcium plays a key role in the control of transmitter release at chemical synapses (Neher, 1998; Südhof, 2013). As transmitter release is a Ca2+-dependent biochemical process, one would expect that both the extent and kinetics of release will depend on Ca2+ concentration. In contrast to this expectation, the time course of release (TCR) at the neuromuscular junction is independent of the extracellular Ca2+ concentration ([Ca2+]o) (Datyner and Gage, 1980; Van der Kloot, 1988; Parnas et al, 1989). Tight coupling might be another factor contributing to the apparent [Ca2+]o independence of the TCR (Yamada and Zucker, 1992). This possibility has not been directly examined
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