Ultrastructural Analysis of the Role of Voltage-Gated Calcium Channel Intracellular Domains in Synaptic Vesicle Tethering at Presynaptic Terminals
Year: 2017
Type: dissertation
Abstract: Chemical synaptic transmission is the main basis by which neurons convey information. This transmission is mediated by the fusion of synaptic vesicles (SVs) and the release of their neurotransmitter payloads across the synapse from a presynaptic neuron onto the receptors of a postsynaptic cell. In response to a depolarizing action potential, voltage-gated calcium channels (CaVs) open and allow the influx of calcium ions (Ca2+) into the presynaptic terminal which triggers the fusion of SVs with the active zone membrane (AZ). Evidence that fusion can be gated by the Ca2+ influx from a single CaV suggests a close coupling of SVs and CaVs likely connected by molecular tethers (Stanley, 1993). We developed a method to easily visualize tethers under electron microscopy (EM) through the osmotic rupture of isolated presynaptic terminals (SSM ghosts) which flushes out obscuring organelles and structures. We observed two classes of SV-to-AZ filaments: SVs within 45 nm of the AZ were often observed to be tethered by multiple, short filaments while SVs beyond 45 nm were tethered invariably by single, long filaments of
Source: TSpace (University of Toronto)
Author: Robert Chen
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2889471286