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Cholesterol Alters the Dynamics of Release in Protein Independent Cell Models for Exocytosis

Journal article
Authors Neda Najafinobar
Lisa J. Mellander
Michael E. Kurczy
Johan Dunevall
Tina B. Angerer
John S. Fletcher
Ann-Sofie Cans
Published in Scientific Reports
Volume 6
Issue Article number: 33702
ISSN 2045-2322
Publication year 2016
Published at Department of Chemistry and Molecular Biology
Language en
Links dx.doi.org/10.1038/srep33702
https://gup.ub.gu.se/file/206211
Keywords individual chromaffin cells, flickering fusion pores, kiss-and-run, membrane tension, bending elasticity, lipid nanotubes, snare proteins, pc12 cells, vesicles, hemifusion
Subject categories Chemical Sciences

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.

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