title: Bayesian analysis of the kinetics of quantal transmitter secretion at the neuromuscular junction.
abstract: The timing of transmitter release from nerve endings is considered nowadays as one of the factors determining the plasticity and efficacy of synaptic transmission. In the neuromuscular junction, the moments of release of individual acetylcholine quanta are related to the synaptic delays of uniquantal endplate currents recorded under conditions of lowered extracellular calcium. Using Bayesian modelling, we performed a statistical analysis of synaptic delays in mouse neuromuscular junction with different patterns of rhythmic nerve stimulation and when the entry of calcium ions into the nerve terminal was modified. We have obtained a statistical model of the release timing which is represented as the summation of two independent statistical distributions. The first of these is the exponentially modified Gaussian distribution. The mixture of normal and exponential components in this distribution can be interpreted as a two-stage mechanism of early and late periods of phasic synchronous secretion. The parameters of this distribution depend on both the stimulation frequency of the motor nerve and the calcium ions' entry conditions. The second distribution was modelled as quasi-uniform, with parameters independent of nerve stimulation frequency and calcium entry. Two different probability density functions for the distribution of synaptic delays suggest at least two independent processes controlling the time course of secretion, one of them potentially involving two stages. The relative contribution of these processes to the total number of mediator quanta released depends differently on the motor nerve stimulation pattern and on calcium ion entry into nerve endings.
authors.affiliation: Kazan Federal University, Kremlevskaya St. 18, Kazan, 420008, Russia.
authors.forename: Anatoly
authors.initials: A
authors.lastname: Saveliev
authors.affiliation: Kazan Federal University, Kremlevskaya St. 18, Kazan, 420008, Russia.|Laboratory of the Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, P.O. Box 30, Kazan, 420111, Russia.
authors.forename: Venera
authors.initials: V
authors.lastname: Khuzakhmetova
authors.affiliation: Kazan Federal University, Kremlevskaya St. 18, Kazan, 420008, Russia.|Laboratory of the Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, P.O. Box 30, Kazan, 420111, Russia.|Kazan National Research Technical University named after A. N. Tupolev, K. Marx St. 10, Kazan, 420111, Russia.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Samigullin
authors.affiliation: Kazan Federal University, Kremlevskaya St. 18, Kazan, 420008, Russia.|Laboratory of the Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, P.O. Box 30, Kazan, 420111, Russia.
authors.forename: Andrey
authors.initials: A
authors.lastname: Skorinkin
authors.affiliation: Kazan Federal University, Kremlevskaya St. 18, Kazan, 420008, Russia.|Laboratory of the Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, P.O. Box 30, Kazan, 420111, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Kovyazina
authors.affiliation: Kazan Federal University, Kremlevskaya St. 18, Kazan, 420008, Russia.|Laboratory of the Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, P.O. Box 30, Kazan, 420111, Russia.|Kazan State Medical University, Butlerov St. 49, Kazan, 420012, Russia.
authors.forename: Eugeny
authors.initials: E
authors.lastname: Nikolsky
authors.affiliation: Kazan Federal University, Kremlevskaya St. 18, Kazan, 420008, Russia. elbukhara@gmail.com.|Laboratory of the Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, P.O. Box 30, Kazan, 420111, Russia. elbukhara@gmail.com.
authors.forename: Ellya
authors.initials: E
authors.lastname: Bukharaeva
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001499:Bayes Theorem; D019256:Cadmium Chloride / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008959:Models, Neurological; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D055366:Synaptic Potentials / Q000187:drug effects / Q000502:physiology*
chemical_list: D018377:Neurotransmitter Agents; D026902:Potassium Channel Blockers; D015761:4-Aminopyridine; D008274:Magnesium; D019256:Cadmium Chloride; D002118:Calcium
keywords: Kinetics of quantal secretion; Neuromuscular junction; Quantal release of neurotransmitter; Statistical model, Bayesian method