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 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).
Gilmanov
Iskander R
IR
Institute of Biochemistry and Biophysics, Russian Academy of Sciences, P.O. Box 30, Kazan, 420111, Russia.
Samigullin
Dmitry V
DV
Vyskocil
Frantisek
F
Nikolsky
Eugeny E
EE
Bukharaeva
Ellya A
EA
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D003198:Computer Simulation; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008954:Models, Biological; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D013997:Time Factors
D015220:Calcium Channels; D002614:Chelating Agents; D018377:Neurotransmitter Agents; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D002118:Calcium