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Developmental regulation of the intracellular Ca 2+ sensitivity of vesicle fusion and Ca 2+ –secretion coupling at the rat calyx of Held
Author(s) -
Kochubey Olexiy,
Han Yunyun,
Schneggenburger Ralf
Publication year - 2009
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.172387
Subject(s) - biophysics , cooperativity , postsynaptic potential , vesicle , coupling (piping) , chemistry , synaptic vesicle , neurotransmission , intracellular , biology , biochemistry , receptor , membrane , materials science , metallurgy
Developmental refinement of synaptic transmission can occur via changes in several pre‐ and postsynaptic factors, but it has been unknown whether the intrinsic Ca 2+ sensitivity of vesicle fusion in the nerve terminal can be regulated during development. Using the calyx of Held, a giant synapse in the auditory pathway, we studied the presynaptic mechanisms underlying the developmental regulation of Ca 2+ –secretion coupling, comparing a time period before, and shortly after the onset of hearing in rats. We found an ∼2‐fold leftward shift in the relationship between EPSC amplitude and presynaptic Ca 2+ current charge ( Q Ca ), indicating that brief presynaptic Ca 2+ currents become significantly more efficient in driving release. Using a Ca 2+ tail current protocol, we also found that the high cooperativity between EPSC amplitude and Q Ca was slightly reduced with development. In contrast, in presynaptic Ca 2+ uncaging experiments, the intrinsic Ca 2+ cooperativity of vesicle fusion was identical, and the intrinsic Ca 2+ sensitivity was slightly reduced with development. This indicates that the significantly enhanced release efficiency of brief Ca 2+ currents must be caused by a tighter co‐localization of Ca 2+ channels and readily releasable vesicles, but not by changes in the intrinsic properties of Ca 2+ ‐dependent release. Using the parameters of the intrinsic Ca 2+ sensitivity measured at each developmental stage, we estimate that during a presynaptic action potential (AP), a given readily releasable vesicle experiences an about 1.3‐fold higher ‘local’ intracellular Ca 2+ concentration ([Ca 2+ ] i ) signal with development. Thus, the data indicate a tightening in the Ca 2+ channel–vesicle co‐localization during development, without a major change in the intrinsic Ca 2+ sensitivity of vesicle fusion.