The coupling between synaptic vesicles and Ca2+ channels determines fast neurotransmitter release.
In order to release neurotransmitter synchronously in response to a presynaptic action potential, synaptic vesicles must be both release competent and located close to presynaptic Ca2+ channels. It has not been shown, however, which of the two is the more decisive factor. We tested this issue at the calyx of Held synapse by combining Ca2+ uncaging and electrophysiological measurements of postsynaptic responses. After depletion of the synaptic vesicles that are responsible for synchronous release during action potentials, uniform elevation of intracellular Ca2+ by Ca2+ uncaging could still elicit rapid release. The Ca2+ sensitivity of remaining vesicles was reduced no more than 2-fold, which is insufficient to explain the slow-down of the kinetics of release (10-fold) observed during a depolarizing pulse. We conclude that recruitment of synaptic vesicles to sites where Ca2+ channels cluster, rather than fusion competence, is a limiting step for rapid neurotransmitter release in response to presynaptic action potentials.
Wadel
Kristian
K
Research Group Biophysics of Synaptic Transmission, Max Planck Institute for Biophysical Chemistry, Göttingen, 37077, Germany.
Neher
Erwin
E
Sakaba
Takeshi
T
D000818:Animals; D000831:Animals, Newborn; D001581:Benzothiadiazines / Q000494:pharmacology; D001933:Brain Stem / Q000166:cytology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D004151:Dipeptides / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007834:Lasers; D008954:Models, Biological; D009474:Neurons / Q000166:cytology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010782:Photolysis; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D050683:R-SNARE Proteins / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology*; D013744:Tetanus Toxin / Q000494:pharmacology; D013997:Time Factors
D001581:Benzothiadiazines; D015220:Calcium Channels; D004151:Dipeptides; D018683:Excitatory Amino Acid Agents; D050683:R-SNARE Proteins; D013744:Tetanus Toxin; C028929:gamma-glutamylglycine; C004639:cyclothiazide; D002118:Calcium