title: Exploring the Membrane Potential of Simple Dual-Membrane Systems as Models for Gap-Junction Channels.
abstract: The conductance of ion channels can be modulated by a transmembrane potential difference, due to alterations on ion-mobility and also by changes in the pore structure. Despite the vast knowledge regarding the influence of voltage on transport properties of ion channels, little attention has been paid to describe, with atomic detail, the modulation of ionic transport in gap-junction channels (GJCs). Hence, molecular dynamics simulations were performed to explore the conductance of simple dual-membrane systems that account for the very basic features of GJCs. In doing so, we studied the influence of different charge distributions in the channel surface on these idealized systems under external electric fields, paying attention to the behavior of the electrostatic potential, ion density, ion currents, and equilibrium properties. Our results demonstrate that the incorporation of a charge distribution akin GJCs decreased anionic currents, favoring the transport of cationic species. Moreover, a thermodynamic characterization of ionic transport in these systems demonstrate the existence of a kinetic barrier that hinders anionic currents, reinforcing the role played by the internal arrangement of charges in GJCs. Overall, our results provide insights at the atomic scale on the effects of charge distributions over ionic transport, constituting a step forward into a better understanding of GJCs.
authors.affiliation: Computational Biology Lab (DLab), Fundación Ciencia & Vida, Santiago, Chile.
authors.forename: Yerko
authors.initials: Y
authors.lastname: Escalona
authors.affiliation: Computational Biology Lab (DLab), Fundación Ciencia & Vida, Santiago, Chile; Centro Interdisciplinario de Neurociencia de Valparaíso (CINV), Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Garate
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio.
authors.forename: Raul
authors.initials: R
authors.lastname: Araya-Secchi
authors.affiliation: Computational Biology Center, IBM Thomas J. Watson Research Center, Yorktown Heights, New York.
authors.forename: Tien
authors.initials: T
authors.lastname: Huynh
authors.affiliation: Computational Biology Center, IBM Thomas J. Watson Research Center, Yorktown Heights, New York.
authors.forename: Ruhong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Computational Biology Lab (DLab), Fundación Ciencia & Vida, Santiago, Chile; Centro Interdisciplinario de Neurociencia de Valparaíso (CINV), Universidad de Valparaíso, Valparaíso, Chile. Electronic address: tomas@dlab.cl.
authors.forename: Tomas
authors.initials: T
authors.lastname: Perez-Acle
mesh_terms: D000818:Animals; D017630:Connexins / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D017136:Ion Transport / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D008567:Membranes, Artificial; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D017630:Connexins; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; C028694:1-palmitoyl-2-oleoylphosphatidylcholine