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A limited contribution of Ca 2+ current facilitation to paired‐pulse facilitation of transmitter release at the rat calyx of Held
Author(s) -
Müller Martin,
Felmy Felix,
Schneggenburger Ralf
Publication year - 2008
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.2008.155838
Subject(s) - facilitation , neural facilitation , voltage clamp , chemistry , biophysics , electrophysiology , neuroscience , neurotransmission , biology , biochemistry , receptor
Recent studies have suggested that transmitter release facilitation at synapses is largely mediated by presynaptic Ca 2+ current facilitation, but the exact contribution of Ca 2+ current facilitation has not been determined quantitatively. Here, we determine the contribution of Ca 2+ current facilitation, and of an increase in the residual free Ca 2+ concentration ([Ca 2+ ] i ) in the nerve terminal, to paired‐pulse facilitation of transmitter release at the calyx of Held. Under conditions of low release probability imposed by brief presynaptic voltage‐clamp steps, transmitter release facilitation at short interstimulus intervals (4 ms) was 227 ± 31% of control, Ca 2+ current facilitation was 113 ± 4% of control, and the peak residual [Ca 2+ ] i was 252 ± 18 n m over baseline. By inferring the ‘local’[Ca 2+ ] i transients that drive transmitter release during these voltage‐clamp stimuli with the help of a kinetic release model, we estimate that Ca 2+ current facilitation contributes to ∼40% to paired‐pulse facilitation of transmitter release. The remaining component of facilitation strongly depends on the build‐up, and on the decay of the residual free [Ca 2+ ] i , but cannot be explained by linear summation of the residual free [Ca 2+ ] i , and the back‐calculated ‘local’[Ca 2+ ] i signal, which only accounts for ∼10% of the total release facilitation. Further voltage‐clamp experiments designed to compensate for Ca 2+ current facilitation demonstrated that about half of the observed transmitter release facilitation remains in the absence of Ca 2+ current facilitation. Our results indicate that paired‐pulse facilitation of transmitter release at the calyx of Held is driven by at least two distinct mechanisms: Ca 2+ current facilitation, and a mechanism independent of Ca 2+ current facilitation that closely tracks the time course of residual free [Ca 2+ ] i .