title: Blocking of an ion channel by a highly charged drug: modeling the effects of applied voltage, electrolyte concentration, and drug concentration.
abstract: We present a simple physical model to estimate the blocked pore probability of an ion channel that can be blocked by a highly charged drug in solution. The model is inspired by recent experimental work on the blocking of the PA(63) channel, involved in the anthrax toxin infection, by a highly charged drug [Karginov PNAS 102, 15075 (2005)]. The drug binding to the pore is highly specific but the strong dependence of blocking on the applied voltage and electrolyte concentration suggests that long range electrostatic interactions are important. Since basic electrostatic concepts rather than detailed molecular models are considered, the microscopic details of the channel blocking are ignored, although the model captures most of the qualitative characteristics of the problem.
authors.affiliation: Departament de Ciències Experimentals, Universitat Jaume I, E-12080 Castelló, Spain.
authors.forename: Marcel
authors.initials: M
authors.lastname: Aguilella-Arzo
authors.forename: Javier
authors.initials: J
authors.lastname: Cervera
authors.forename: Patricio
authors.initials: P
authors.lastname: Ramírez
authors.forename: Salvador
authors.initials: S
authors.lastname: Mafé
mesh_terms: D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry / Q000379:methods; D004573:Electrolytes / Q000737:chemistry; D004574:Electromagnetic Fields; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008954:Models, Biological; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D004573:Electrolytes; D007473:Ion Channels; D004364:Pharmaceutical Preparations