title: Facilitation through buffer saturation: constraints on endogenous buffering properties.
abstract: Synaptic facilitation (SF) is a ubiquitous form of short-term plasticity, regulating synaptic dynamics on fast timescales. Although SF is known to depend on the presynaptic accumulation of Ca(2+), its precise mechanism is still under debate. Recently it has been shown that at certain central synapses SF results at least in part from the progressive saturation of an endogenous Ca(2+) buffer (Blatow et al., 2003), as proposed by Klingauf and Neher (1997). Using computer simulations, we study the magnitude of SF that can be achieved by a buffer saturation mechanism (BSM), and explore its dependence on the endogenous buffering properties. We find that a high SF magnitude can be obtained either by a global saturation of a highly mobile buffer in the entire presynaptic terminal, or a local saturation of a completely immobilized buffer. A characteristic feature of BSM in both cases is that SF magnitude depends nonmonotonically on the buffer concentration. In agreement with results of Blatow et al. (2003), we find that SF grows with increasing distance from the Ca(2+) channel cluster, and increases with increasing external Ca(2+), [Ca(2+)](ext), for small levels of [Ca(2+)](ext). We compare our modeling results with the experimental properties of SF at the crayfish neuromuscular junction, and find that the saturation of an endogenous mobile buffer can explain the observed SF magnitude and its supralinear accumulation time course. However, we show that the BSM predicts slowing of the SF decay rate in the presence of exogenous Ca(2+) buffers, contrary to experimental observations at the crayfish neuromuscular junction. Further modeling and data are required to resolve this aspect of the BSM.
authors.affiliation: Department of Mathematical Sciences, New Jersey Institute of Technology, Newark, New Jersey 07102, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Matveev
authors.forename: Robert S
authors.initials: RS
authors.lastname: Zucker
authors.forename: Arthur
authors.initials: A
authors.lastname: Sherman
mesh_terms: D000818:Animals; D003400:Astacoidea; D001665:Binding Sites; D001703:Biophysics / Q000379:methods; D002021:Buffers; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D003198:Computer Simulation; D005456:Fluorescent Dyes / Q000494:pharmacology; D016257:Fura-2 / Q000494:pharmacology; D007700:Kinetics; D008962:Models, Theoretical; D009469:Neuromuscular Junction; D013997:Time Factors
chemical_list: D002021:Buffers; D015220:Calcium Channels; D005456:Fluorescent Dyes; D002118:Calcium; D016257:Fura-2