Modeling study of the effects of membrane surface charge on calcium microdomains and neurotransmitter release.

Abstract:

:Synchronous neurotransmitter release is mediated by the opening of voltage-gated Ca(2+) channels and the build-up of submembrane Ca(2+) microdomains. Previous models of Ca(2+) microdomains have neglected possible electrostatic interactions between Ca(2+) ions and negative surface charges on the inner leaflet of the plasma membrane. To address the effects of these interactions, we built a computational model of ion electrodiffusion described by the Nernst-Planck and Poisson equations. We found that inclusion of a negative surface charge significantly alters the spatial characteristics of Ca(2+) microdomains. Specifically, close to the membrane, Ca(2+) ions accumulate, as expected from the strong electrostatic attraction exerted on positively charged Ca(2+) ions. Farther away from the membrane, increasing the surface charge density results in a reduction of the Ca(2+) concentration because of the preferential spread of Ca(2+) ions along lateral directions. The model also predicts that the negative surface charge will decrease the spatial gradient of the Ca(2+) microdomain in the lateral direction, resulting in increased overlap of microdomains originating from different Ca(2+) channels. Finally, we found that surface charge increases the probability of vesicle release if the Ca(2+) sensor is located within the electrical double layer, whereas this probability is decreased if the Ca(2+) sensor lies at greater distances from the membrane. Our data suggest that membrane surface charges exert a significant influence on the profile of Ca(2+) microdomains, and should be taken into account in models of neurotransmitter release.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Catacuzzeno L,Fioretti B,Franciolini F

doi

10.1529/biophysj.107.124909

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

2160-71

issue

5

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(08)78365-6

journal_volume

95

pub_type

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