title: 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.
authors.affiliation: Dipartimento di Biologia Cellulare e Ambientale, Università di Perugia, Perugia, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Catacuzzeno
authors.forename: Bernard
authors.initials: B
authors.lastname: Fioretti
authors.forename: Fabio
authors.initials: F
authors.lastname: Franciolini
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology; D021962:Membrane Microdomains / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology*; D008954:Models, Biological; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D055672:Static Electricity
chemical_list: D015220:Calcium Channels; D018377:Neurotransmitter Agents; D002118:Calcium