Modeling of quantal neurotransmitter release kinetics in the presence of fixed and mobile calcium buffers
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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).
KeywordsNeuromuscular junction Mathematical modeling Time course of secretion Calcium buffers
time course of secretion
1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid tetrakis acetoxymethyl ester
We thank Dr. Maria Bykhovskaia and Dr. Andrey Skorinkin for critical reading of the manuscript. Supported by GAAVA5011411, GACR305/02/1333, and MSMT11310003 for FV, by RFBR 08-04-00923, Russian Scientific Schools—4177.2008.4 for EN, by “Russian Science Support Foundation” for DS, by US Civilian Research and Development Foundation (RUB1-2823-KA06) for EB and DS.
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