title: Protein structure and ionic selectivity in calcium channels: selectivity filter size, not shape, matters.
abstract: Calcium channels have highly charged selectivity filters (4 COO(-) groups) that attract cations in to balance this charge and minimize free energy, forcing the cations (Na(+) and Ca(2+)) to compete for space in the filter. A reduced model was developed to better understand the mechanism of ion selectivity in calcium channels. The charge/space competition (CSC) mechanism implies that Ca(2+) is more efficient in balancing the charge of the filter because it provides twice the charge as Na(+) while occupying the same space. The CSC mechanism further implies that the main determinant of Ca(2+) versus Na(+) selectivity is the density of charged particles in the selectivity filter, i.e., the volume of the filter (after fixing the number of charged groups in the filter). In this paper we test this hypothesis by changing filter length and/or radius (shape) of the cylindrical selectivity filter of our reduced model. We show that varying volume and shape together has substantially stronger effects than varying shape alone with volume fixed. Our simulations show the importance of depletion zones of ions in determining channel conductance calculated with the integrated Nernst-Planck equation. We show that confining the protein side chains with soft or hard walls does not influence selectivity.
authors.affiliation: Department of Physical Chemistry, University of Pannonia, Veszprém, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Malasics
authors.forename: Dirk
authors.initials: D
authors.lastname: Gillespie
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Nonner
authors.forename: Douglas
authors.initials: D
authors.lastname: Henderson
authors.forename: Bob
authors.initials: B
authors.lastname: Eisenberg
authors.forename: Dezso
authors.initials: D
authors.lastname: Boda
mesh_terms: D000818:Animals; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D008956:Models, Chemical; D008958:Models, Molecular; D017434:Protein Structure, Tertiary / Q000502:physiology; D012964:Sodium / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D020746:Calcium Channels, L-Type; D012964:Sodium; D002118:Calcium