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Experimental and Monte Carlo studies of Ca2+ channel function and fast transmitter release at presynaptic active zones of the frog neuromuscular junction

Luo, Fujun (2009) Experimental and Monte Carlo studies of Ca2+ channel function and fast transmitter release at presynaptic active zones of the frog neuromuscular junction. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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During fast chemical synaptic transmission, neurotransmitter release is triggered by calcium (Ca2+) influx through voltage-gated Ca2+ channels (VGCCs) opened by an action potential (AP) at the nerve terminal. The magnitude and time course of neurotransmitter release is critically determined by the coupling between Ca2+ channels and synaptic vesicles. Studies of the quantitative dependence of transmitter release on the number of VGCCs provide important information for our understanding of the mechanisms that underlie the control and modulation of presynaptic release probability and kinetics. Using high-resolution calcium imaging techniques and variance analysis, I have determined the number of functional VGCCs within individual active zones (AZs) of the adult frog neuromuscular junction (NMJ) and their opening probability in response to single AP stimulation. The results have shown that the average number of VGCCs within individual active zones was relatively small (~28) and the average opening probability of individual Ca2+ channels during a presynaptic AP was very low (~0.24). Therefore, it is predicted that an action potential induced opening of relatively few Ca2+ channels in a single active zone. Furthermore, by combining pharmacological channel block, calcium imaging, postsynaptic recording, and 3D Monte Carlo diffusion-reaction simulations, I have studied the coupling of single Ca2+ channel openings to the triggering of vesicle fusion. I have provided evidence that Ca2+ entry through single open Ca2+ channels at the nerve terminal can be imaged directly and that such Ca2+ flux is sufficient to trigger synaptic vesicle fusion. I have further shown that following a single AP, the Ca2+ influx through a single open channel plays the predominant role in evoking neurotransmitter release, while Ca2+ ions derived from a collection of open Ca2+ channels are rarely required for vesicle exocytosis at this synapse.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Luo, Fujunful1@pitt.eduFUL1
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMeriney, Stephenmeriney@pitt.eduMERINEY
Committee MemberBi,
Committee MemberLin,
Committee MemberStiles,
Committee MemberJohnson, Jonjjohnson@pitt.eduJJOHNSON
Committee MemberUrban,
Date: 30 September 2009
Date Type: Completion
Defense Date: 23 June 2009
Approval Date: 30 September 2009
Submission Date: 13 August 2009
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Neuroscience
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: active zone; neuromuscular junction; optical fluctuation analysis; transmitter release; voltage-gated calcium channel
Other ID:, etd-08132009-133311
Date Deposited: 10 Nov 2011 19:59
Last Modified: 15 Nov 2016 13:49


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