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 Jjournal_title
Biophysical journalauthors
Catacuzzeno L,Fioretti B,Franciolini Fdoi
10.1529/biophysj.107.124909subject
Has Abstractpub_date
2008-09-01 00:00:00pages
2160-71issue
5eissn
0006-3495issn
1542-0086pii
S0006-3495(08)78365-6journal_volume
95pub_type
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