title: Cholesterol Alters the Dynamics of Release in Protein Independent Cell Models for Exocytosis.
abstract: Neurons communicate via an essential process called exocytosis. Cholesterol, an abundant lipid in both secretory vesicles and cell plasma membrane can affect this process. In this study, amperometric recordings of vesicular dopamine release from two different artificial cell models created from a giant unilamellar liposome and a bleb cell plasma membrane, show that with higher membrane cholesterol the kinetics for vesicular release are decelerated in a concentration dependent manner. This reduction in exocytotic speed was consistent for two observed modes of exocytosis, full and partial release. Partial release events, which only occurred in the bleb cell model due to the higher tension in the system, exhibited amperometric spikes with three distinct shapes. In addition to the classic transient, some spikes displayed a current ramp or plateau following the maximum peak current. These post spike features represent neurotransmitter release from a dilated pore before constriction and show that enhancing membrane rigidity via cholesterol adds resistance to a dilated pore to re-close. This implies that the cholesterol dependent biophysical properties of the membrane directly affect the exocytosis kinetics and that membrane tension along with membrane rigidity can influence the fusion pore dynamics and stabilization which is central to regulation of neurochemical release.
authors.affiliation: Department of Chemistry and Chemical Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.
authors.forename: Neda
authors.initials: N
authors.lastname: Najafinobar
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96 Gothenburg, Sweden.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Mellander
authors.affiliation: Department of Chemistry and Chemical Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Kurczy
authors.affiliation: Department of Chemistry and Chemical Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Dunevall
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96 Gothenburg, Sweden.
authors.forename: Tina B
authors.initials: TB
authors.lastname: Angerer
authors.affiliation: Department of Chemistry and Chemical Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.
authors.forename: John S
authors.initials: JS
authors.lastname: Fletcher
authors.affiliation: Department of Chemistry and Chemical Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.
authors.forename: Ann-Sofie
authors.initials: AS
authors.lastname: Cans
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats
chemical_list: D002784:Cholesterol