Residual bound Ca2+ can account for the effects of Ca 2+ buffers on synaptic facilitation

Victor Matveev, Richard Bertram, Arthur Sherman

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Facilitation is a transient stimulation-induced increase in synaptic response, a ubiquitous form of short-term synaptic plasticity that can regulate synaptic transmission on fast time scales. In their pioneering work, Katz and Miledi and Rahamimoff demonstrated the dependence of facilitation on presynaptic Ca2+ influx and proposed that facilitation results from the accumulation of residual Ca2+ bound to vesicle release triggers. However, this bound Ca2+ hypothesis appears to contradict the evidence that facilitation is reduced by exogenous Ca2+ buffers. This conclusion led to a widely held view that facilitation must depend solely on the accumulation of Ca2+ in free form. Here we consider a more realistic implementation of the bound Ca2+ mechanism, taking into account spatial diffusion of Ca2+, and show that a model with slow Ca 2+ unbinding steps can retain sensitivity to free residual Ca 2+. We demonstrate that this model agrees with the facilitation accumulation time course and its biphasic decay exhibited by the crayfish inhibitor neuromuscular junction (NMJ) and relies on fewer assumptions than the most recent variants of the free residual Ca2+ hypothesis. Further, we show that the bound Ca2+ accumulation is consistent with Kamiya and Zucker's experimental results, which revealed that photolytic liberation of a fast Ca2+ buffer decreases the synaptic response within milliseconds. We conclude that Ca2+ binding processes with slow unbinding times (tens to hundreds of milliseconds) constitute a viable mechanism of synaptic facilitation at some synapses and discuss the experimental evidence for such a mechanism.

Original languageEnglish (US)
Pages (from-to)3389-3397
Number of pages9
JournalJournal of neurophysiology
Volume96
Issue number6
DOIs
StatePublished - Dec 2006

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

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