title: Potential of mean force calculations on an L-type calcium channel model.
abstract: To understand the mechanisms of Na(+)/Li(+) permeation at submicromolar Ca(2+) concentrations, Na(+)/Li(+) blocking at higher Ca(2+) concentrations (10(-6)-10(-4) M) and Ca(2+) permeation at millimolar Ca(2+) concentrations, we used our recently described L-type calcium channel model. For this purpose, we obtained potential of mean force (pmf) curves for the position change of one Na(+) and one Ca(2+) ion inside the channel and for the position change of a second Ca(2+) ion when the EEEE locus is coordinated to Ca(2+). The pmf curves suggest that (i) at submicromolar Ca(2+) concentrations, because of the low velocity of Ca(2+) entry in the channel, monovalent ion flux occurs; (ii) at Ca(2+) concentrations between 10(-6) and 10(-4) M, thermodynamic equilibrium between the channel and Ca(2+) is achieved; as the coordination of Ca(2+) with the locus is more favorable than the coordination of Na(+), the monovalent ion flux is blocked; and (iii) to put a second Ca(2+) ion inside the channel at an appropriate rate, the Ca(2+) concentration should reach millimolar levels. Nevertheless, the entry of a second Ca(2+) is thermodynamically unfavorable, indicating that the competition of two Ca(2+) ions for the locus leads to Ca(2+) permeation.
authors.affiliation: Physical Organic Chemistry Group, Departamento de Química Orgânica, Instituto de Química, UFRJ, Bloco A, Sala 609, Cidade Universitária, Ilha do Fundão, CT, RJ 21949-900, Rio de Janeiro, Brazil. gbarreiro@wesleyan.edu
authors.forename: Gabriela
authors.initials: G
authors.lastname: Barreiro
authors.forename: Cristiano Ruch Werneck
authors.initials: CR
authors.lastname: Guimarães
authors.forename: Ricardo Bicca
authors.initials: RB
authors.lastname: de Alencastro
mesh_terms: D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000737:chemistry* / Q000378:metabolism; D008094:Lithium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D020746:Calcium Channels, L-Type; D008094:Lithium; D012964:Sodium; D002118:Calcium