HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 96/6/3389    most recent 00101.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Matveev, V. Articles by Sherman, A. Search for Related Content PubMed PubMed Citation Articles by Matveev, V. Articles by Sherman, A.

Residual Bound Ca²⁺ Can Account for the Effects of Ca²⁺ Buffers on Synaptic Facilitation

¹Department of Mathematical Sciences, New Jersey Institute of Technology, Newark, New Jersey; ²Department of Mathematics and Programs in Neuroscience and Molecular Biophysics, Florida State University, Tallahassee, Florida; and ³Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

Submitted 30 January 2006; accepted in final form 1 September 2006

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 Ca²⁺ unbinding steps can retain sensitivity to free residual Ca²⁺. 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.

This article has been cited by other articles:

				V. Matveev, R. Bertram, and A. Sherman Ca2+ Current versus Ca2+ Channel Cooperativity of Exocytosis J. Neurosci., September 30, 2009; 29(39): 12196 - 12209. [Abstract] [Full Text] [PDF]

				M. Muller, F. Felmy, and R. Schneggenburger A limited contribution of Ca2+ current facilitation to paired-pulse facilitation of transmitter release at the rat calyx of Held J. Physiol., November 15, 2008; 586(22): 5503 - 5520. [Abstract] [Full Text] [PDF]

				S. R. Williams and S. E. Atkinson Pathway-specific use-dependent dynamics of excitatory synaptic transmission in rat intracortical circuits J. Physiol., December 15, 2007; 585(3): 759 - 777. [Abstract] [Full Text] [PDF]