Abstract
A theoretical analysis of some of the relevant factors influencing the calcium time course and the strength and timing of release probabilities of vesicles evoked by an action potential in a calyx-type active zone is presented in this paper. In particular, our study focus on the comparison of cooperative vs non-cooperative calcium binding by the release site and the effect of the number of Ca(2+) binding sites on the calcium sensitivity for release. Regarding the comparison of cooperative and non-cooperative kinetic schemes, our simulations show that quite different results are obtained when considering one or another: a reduction in the release probability of more than a 50% is obtained when considering the cooperative kinetic scheme. Also, a delay in the average time for release appears when using this model for the calcium sensor. Our study also shows that a non-cooperative kinetic binding scheme gives rise to a well defined average calcium level for release assuming that the same kinetic constants are considered for all the sites. Our results also suggest that the central value of the calcium sensitivity for release depends on the number of binding sites N and the dissociation constant KD with a scaling law depending on NKD.
Highlights
Release of neurotransmitter by small clean granules in synapses is known to depend on the Ca2+ concentration
We study some of the main elements influencing granule fusion in an active zone of a presynaptic terminal model: the calyx of Held, since this is a large synapse widely used as a model to study stimulus-secretion coupling in neurotransmitter release
We simulate the calcium entry corresponding to a typical action potential (AP); for this purpose, the twostate kinetic model proposed in [5] is considered for the calcium channels
Summary
Release of neurotransmitter by small clean granules (size ∼45 nm of diameter) in synapses is known to depend on the Ca2+ concentration.
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