Modeling of quantal neurotransmitter release kinetics in the presence of fixed and mobile calcium buffers

The local calcium concentration in the active zone of secretion determines the number and kinetics of neurotransmitter quanta released after the arrival of a nerve action potential in chemical synapses. The small size of mammalian neuromuscular junctions does not allow direct measurement of the correlation between calcium influx, the state of endogenous calcium buffers determining the local concentration of calcium and the time course of quanta exocytosis. In this work, we used computer modeling of quanta release kinetics with various levels of calcium influx and in the presence of endogenous calcium buffers with varying mobilities. The results of this modeling revealed the desynchronization of quanta release under low calcium influx in the presence of an endogenous fixed calcium buffer, with a diffusion coefficient much smaller than that of free Ca2+, and synchronization occurred upon adding a mobile buffer. This corresponds to changes in secretion time course parameters found experimentally (Samigullin et al., Physiol Res 54:129–132, 2005; Bukharaeva et al., J Neurochem 100:939–949, 2007).

[1]  F. Dodge,et al.  Co‐operative action of calcium ions in transmitter release at the neuromuscular junction , 1967, The Journal of physiology.

[2]  E. Stuenkel,et al.  Regulation of intracellular calcium and calcium buffering properties of rat isolated neurohypophysial nerve endings. , 1994, The Journal of physiology.

[3]  W. Kloot.  The kinetics of quantal releases during end-plate currents at the frog neuromuscular junction. , 1988 .

[4]  E. Neher,et al.  The use of fura-2 for estimating ca buffers and ca fluxes , 1995, Neuropharmacology.

[5]  B. Sakmann,et al.  Calcium Secretion Coupling at Calyx of Held Governed by Nonuniform Channel–Vesicle Topography , 2002, The Journal of Neuroscience.

[6]  Jen-Wei Lin,et al.  Probing the endogenous Ca2+ buffers at the presynaptic terminals of the crayfish neuromuscular junction. , 2005, Journal of neurophysiology.

[7]  S. Thesleff.  Transmitter release at the neuromuscular junction. , 1988, Puerto Rico health sciences journal.

[8]  R S Zucker,et al.  Effects of mobile buffers on facilitation: experimental and computational studies. , 2000, Biophysical journal.

[9]  Dirk Dietrich,et al.  Endogenous Ca2+ Buffer Concentration and Ca2+ Microdomains in Hippocampal Neurons , 2005, The Journal of Neuroscience.

[10]  R. Schneggenburger,et al.  Parvalbumin Is a Mobile Presynaptic Ca2+ Buffer in the Calyx of Held that Accelerates the Decay of Ca2+ and Short-Term Facilitation , 2007, The Journal of Neuroscience.

[11]  E. Neher,et al.  Presynaptic calcium and control of vesicle fusion , 2005, Current Opinion in Neurobiology.

[12]  D. Hilt,et al.  The S-100 Protein Family: A Biochemical and Functional Overview , 1991 .

[13]  G. Fritzsch,et al.  Comparison of the enhanced steady-state diffusion of calcium by calbindin-D9K and calmodulin: possible importance in intestinal calcium absorption. , 1989, Cell calcium.

[14]  W G Regehr,et al.  Timing of synaptic transmission. , 1999, Annual review of physiology.

[15]  Jen-Wei Lin,et al.  Probing the Endogenous Ca 2 Buffers at the Presynaptic Terminals of the Crayfish Neuromuscular Junction , 2005 .

[16]  J W Moore,et al.  Dynamics of intracellular calcium and its possible relationship to phasic transmitter release and facilitation at the frog neuromuscular junction , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[17]  V. Shahrezaei,et al.  Ca2+ from One or Two Channels Controls Fusion of a Single Vesicle at the Frog Neuromuscular Junction , 2006, The Journal of Neuroscience.

[18]  E. Neher,et al.  Modeling buffered Ca2+ diffusion near the membrane: implications for secretion in neuroendocrine cells. , 1997, Biophysical journal.

[19]  W. Gibson,et al.  The probability of quantal secretion near a single calcium channel of an active zone. , 2000, Biophysical journal.

[20]  Jen-Wei Lin,et al.  Relative distribution of Ca2+ channels at the crayfish inhibitory neuromuscular junction. , 2004, Journal of neurophysiology.

[21]  B. Katz,et al.  The role of calcium in neuromuscular facilitation , 1968, The Journal of physiology.

[22]  F. Vyskocil,et al.  Protein kinase A cascade regulates quantal release dispersion at frog muscle endplate , 2002, The Journal of physiology.

[23]  E Neher,et al.  Time course of Ca2+ concentration triggering exocytosis in neuroendocrine cells. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[24]  E Neher,et al.  Mobile and immobile calcium buffers in bovine adrenal chromaffin cells. , 1993, The Journal of physiology.

[25]  G. Bi,et al.  Synaptic Modifications in Cultured Hippocampal Neurons: Dependence on Spike Timing, Synaptic Strength, and Postsynaptic Cell Type , 1998, The Journal of Neuroscience.

[26]  B. Katz,et al.  The measurement of synaptic delay, and the time course of acetylcholine release at the neuromuscular junction , 1965, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[27]  I. Parnas,et al.  Neurotransmitter release and its facilitation in crayfish , 1986, Pflügers Archiv.

[28]  F. Sala,et al.  Calcium diffusion modeling in a spherical neuron. Relevance of buffering properties. , 1990, Biophysical journal.

[29]  E. Nikolsky,et al.  Calcium dependence of uni-quantal release latencies and quantal content at mouse neuromuscular junction. , 2005, Physiological research.

[30]  Suk-Ho Lee,et al.  Kinetics of Ca2+ binding to parvalbumin in bovine chromaffin cells: implications for [Ca2+] transients of neuronal dendrites , 2000, The Journal of physiology.

[31]  W. Yamada,et al.  Time course of transmitter release calculated from simulations of a calcium diffusion model. , 1992, Biophysical journal.

[32]  A. Marty,et al.  Developmental Changes in Parvalbumin Regulate Presynaptic Ca2+ Signaling , 2005, The Journal of Neuroscience.

[33]  J. Connor,et al.  Calcium regulation by and buffer capacity of molluscan neurons during calcium transients. , 1988, Cell calcium.

[34]  Ralf Schneggenburger,et al.  Intracellular calcium dependence of transmitter release rates at a fast central synapse , 2000, Nature.

[35]  C. Heizmann.  Novel Calcium-Binding Proteins , 1991, Springer Berlin Heidelberg.

[36]  Shin Ishii,et al.  Local signaling with molecular diffusion as a decoder of Ca2+ signals in synaptic plasticity , 2005, Molecular Systems Biology.

[37]  Amparo Gil,et al.  Modeling study of exocytosis in neuroendocrine cells: influence of the geometrical parameters. , 2000, Biophysical journal.

[38]  R. Zucker,et al.  Facilitation through buffer saturation: constraints on endogenous buffering properties. , 2004, Biophysical journal.

[39]  I. Parnas,et al.  Neurotransmitter release and its facilitation in crayfish , 1982, Pflügers Archiv.

[40]  B W Kooi,et al.  Diffusion barriers limit the effect of mobile calcium buffers on exocytosis of large dense cored vesicles. , 1999, Biophysical journal.

[41]  Micha E. Spira,et al.  Low Mobility of the Ca2+ Buffers in Axons of Cultured Aplysia Neurons , 1997, Neuron.

[42]  Jen-Wei Lin,et al.  Modulation of synaptic delay during synaptic plasticity , 2002, Trends in Neurosciences.

[43]  Hartmut Schmidt,et al.  Mutational analysis of dendritic Ca2+ kinetics in rodent Purkinje cells: role of parvalbumin and calbindin D28k , 2003, The Journal of physiology.

[44]  George J. Augustine,et al.  Neuronal Ca2+ signalling takes the local route , 1992, Current Opinion in Neurobiology.

[45]  C. Stevens,et al.  The kinetics of transmitter release at the frog neuromuscular junction , 1972, The Journal of physiology.

[46]  B. Soucek.  Influence of the latency fluctuations and the quantal process of transmitter release on the end-plate potentials' amplitude distribution. , 1971, Biophysical Journal.

[47]  G. Augustine.  How does calcium trigger neurotransmitter release? , 2001, Current Opinion in Neurobiology.

[48]  E Neher,et al.  Calcium requirements for secretion in bovine chromaffin cells. , 1992, The Journal of physiology.

[49]  H. Markram,et al.  Regulation of Synaptic Efficacy by Coincidence of Postsynaptic APs and EPSPs , 1997, Science.

[50]  F. Vyskočil,et al.  Modelling endplate currents: dependence on quantum secretion probability and decay of miniature current , 2004, European Biophysics Journal.

[51]  Andrei Rozov,et al.  Presynaptic Ca2+ dynamics, Ca2+ buffers and synaptic efficacy. , 2005, Cell calcium.

[52]  L. Magazanik,et al.  Modulation of the kinetics of evoked quantal release at mouse neuromuscular junctions by calcium and strontium , 2007, Journal of neurochemistry.

[53]  Arthur Sherman,et al.  New and corrected simulations of synaptic facilitation. , 2002, Biophysical journal.

[54]  M. Pinter,et al.  Time courses of calcium and calcium-bound buffers following calcium influx in a model cell. , 1993, Biophysical journal.

[55]  V. Shahrezaei,et al.  Consequences of molecular-level Ca2+ channel and synaptic vesicle colocalization for the Ca2+ microdomain and neurotransmitter exocytosis: a monte carlo study. , 2004, Biophysical journal.

[56]  W. G. Van der Kloot.  The kinetics of quantal releases during end‐plate currents at the frog neuromuscular junction. , 1988, The Journal of physiology.