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The Hodgkin–Huxley–Katz Prize Lecture
Author(s) -
Meinrenken Christoph J.,
Borst J. Gerard G.,
Sakmann Bert
Publication year - 2003
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 - 10.1111/j..2003.t01-1-00665.x
Subject(s) - neuroscience , postsynaptic potential , ribbon synapse , synapse , active zone , neurotransmission , biophysics , chemistry , biology , synaptic vesicle , vesicle , biochemistry , receptor , membrane
During the last decade, advances in experimental techniques and quantitative modelling have resulted in the development of the calyx of Held as one of the best preparations in which to study synaptic transmission. Here we review some of these advances, including simultaneous recording of pre‐ and postsynaptic currents, measuring the Ca 2+ sensitivity of transmitter release, reconstructing the 3‐D anatomy at the electron microscope (EM) level, and modelling the buffered diffusion of Ca 2+ in the nerve terminal. An important outcome of these studies is an improved understanding of the Ca 2+ signal that controls phasic transmitter release. This article illustrates the spatial and temporal aspects of the three main steps in the presynaptic signalling cascade: Ca 2+ influx through voltage‐gated calcium channels, buffered Ca 2+ diffusion from the channels to releasable vesicles, and activation of the Ca 2+ sensor for release. Particular emphasis is placed on how presynaptic Ca 2+ buffers affect the Ca 2+ signal and thus the amplitude and time course of the release probability. Since many aspects of the signalling cascade were first conceived with reference to the squid giant presynaptic terminal, we include comparisons with the squid model and revisit some of its implications. Whilst the characteristics of buffered Ca 2+ diffusion presented here are based on the calyx of Held, we demonstrate the circumstances under which they may be valid for other nerve terminals at mammalian CNS synapses.