title: Residual bound Ca2+ can account for the effects of Ca2+ buffers on synaptic facilitation.
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 Ca(2+) influx and proposed that facilitation results from the accumulation of residual Ca(2+) bound to vesicle release triggers. However, this bound Ca(2+) hypothesis appears to contradict the evidence that facilitation is reduced by exogenous Ca(2+) buffers. This conclusion led to a widely held view that facilitation must depend solely on the accumulation of Ca(2+) in free form. Here we consider a more realistic implementation of the bound Ca(2+) mechanism, taking into account spatial diffusion of Ca(2+), 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 Ca(2+) hypothesis. Further, we show that the bound Ca(2+) accumulation is consistent with Kamiya and Zucker's experimental results, which revealed that photolytic liberation of a fast Ca(2+) buffer decreases the synaptic response within milliseconds. We conclude that Ca(2+) 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.
authors.affiliation: New Jersey Institute of Technology, University Heights, Newark, NJ 07102, USA. matveev@oak.njit.edu
authors.forename: Victor
authors.initials: V
authors.lastname: Matveev
authors.forename: Richard
authors.initials: R
authors.lastname: Bertram
authors.forename: Arthur
authors.initials: A
authors.lastname: Sherman
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000465:Algorithms; D000818:Animals; D003400:Astacoidea / Q000502:physiology*; D002021:Buffers; D002118:Calcium / Q000378:metabolism* / Q000502:physiology*; D004058:Diffusion; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008959:Models, Neurological; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: D002021:Buffers; D002118:Calcium