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

Abstract

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 Ca(2+), 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).

Prenatal hyperhomocysteinemia induces oxidative stress and accelerates ‘aging’ of mammalian neuromuscular synapses

“…High level of asynchrony in newborns observed in central and peripheral synapses are mainly explained by the poor maturity of the mechanisms controlling the intracellular Ca 2+ concentration (Chang and Mennerick, 2010). In fact, developmental upregulation of endogenous Ca 2+ buffering proteins, such as calretinin and parvalbumin, low Ca 2+ affinity of synaptotagmins and reduced efficiency of Ca 2+ buffers were demonstrated in immature synapses (Iwasaki et al, 2000; Chuhma et al, 2001; Gilmanov et al, 2008). In addition, during early stages of ontogenesis along with P/Q type Ca 2+ channels, L‐type Ca channels with slower kinetics and a more distant location to active zones are involved in transmitter release (Nudler et al, 2003; Khuzakhmetova et al, 2016).…”

Kinetics of acetylcholine quanta release at the neuromuscular junction during high‐frequency nerve stimulation

“…A modification of the release time course, particularly an increase of asynchrony of the secretion of quanta, results in a prolongation of the rising phase of the multiquantal signal and in a decrease of its amplitude (Sabatini & Regehr, 1999; Nikolsky et al. , 2004; Gilmanov et al. , 2008).…”

“…, 2004; Lin et al. , 2005; Gilmanov et al. , 2008) and (iv) modulation of the secretory process via intracellular signaling (Wang & Kaczmarek, 1998; Bukharaeva et al.…”

Exocytotic dynamics and calcium cooperativity effects in the calyx of Held synapse: a modelling study

“…Apart from some of the previously cited references, there is a number of theoretical studies on the influence of calcium on the neurotransmitter release dynamics: for Monte Carlo schemes see the classical reference of Bartol et al (1991), on vertebrate neuromuscular junction, or Shahrezaei and Delaney (2004). For a very recent study in mammalian neuromuscular junctions see Gilmanov et al (2008). Some of these studies assume important simplifications regarding the geometry of the system or the mechanisms involved, as in Gilmanov et al (2008), where just a single channel is considered in the simulations.…”

“…For a very recent study in mammalian neuromuscular junctions see Gilmanov et al (2008). Some of these studies assume important simplifications regarding the geometry of the system or the mechanisms involved, as in Gilmanov et al (2008), where just a single channel is considered in the simulations.…”