title: Nanodomain coupling explains Ca²⁺ independence of transmitter release time course at a fast central synapse.
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.
authors.affiliation: IST Austria (Institute of Science and Technology Austria), Klosterneuburg, Austria.
authors.forename: Itaru
authors.initials: I
authors.lastname: Arai
authors.affiliation: IST Austria (Institute of Science and Technology Austria), Klosterneuburg, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Jonas
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D005260:Female; D008297:Male; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011689:Purkinje Cells / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D013997:Time Factors
chemical_list: D015220:Calcium Channels; D018377:Neurotransmitter Agents; D002118:Calcium
keywords: Ca2+ channels; GABAergic synapses; cerebellar basket cells; mouse; nanodomain coupling; neuroscience; release sensors; time course of transmitter release