A dual-Ca2+-sensor model for neurotransmitter release in a central synapse.
Ca2+-triggered synchronous neurotransmitter release is well described, but asynchronous release-in fact, its very existence-remains enigmatic. Here we report a quantitative description of asynchronous neurotransmitter release in calyx-of-Held synapses. We show that deletion of synaptotagmin 2 (Syt2) in mice selectively abolishes synchronous release, allowing us to study pure asynchronous release in isolation. Using photolysis experiments of caged Ca2+, we demonstrate that asynchronous release displays a Ca2+ cooperativity of approximately 2 with a Ca2+ affinity of approximately 44 microM, in contrast to synchronous release, which exhibits a Ca2+ cooperativity of approximately 5 with a Ca2+ affinity of approximately 38 muM. Our results reveal that release triggered in wild-type synapses at low Ca2+ concentrations is physiologically asynchronous, and that asynchronous release completely empties the readily releasable pool of vesicles during sustained elevations of Ca2+. We propose a dual-Ca2+-sensor model of release that quantitatively describes the contributions of synchronous and asynchronous release under conditions of different presynaptic Ca2+ dynamics.
Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. Jianyuan.Sun@UTSouthwestern.edu
Jianyuan
J
Sun
Zhiping P
ZP
Pang
Dengkui
D
Qin
Abigail T
AT
Fahim
Roberto
R
Adachi
Thomas C
TC
Südhof
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010782:Photolysis; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D050861:Synaptotagmin II / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
D018377:Neurotransmitter Agents; D050861:Synaptotagmin II; D002118:Calcium