title: Ion channel drug potency assay with an artificial bilayer chip.
abstract: The potency of pharmaceutical compounds acting on ion channels can be determined through measurements of ion channel conductance as a function of compound concentration. We have developed an artificial lipid bilayer chip for simple, fast, and high-yield measurement of ion channel conductance with simultaneous solution perfusion. Here we show the application of this chip to the measurement of the mammalian cold and menthol receptor TRPM8. Ensemble measurements of TRPM8 as a function of concentration of menthol and 2-aminoethoxydiphenyl borate (2-APB) enabled efficient determination of menthol's EC(50) (111.8 μM ± 2.4 μM) and 2-APB's IC(50) (4.9 μM ± 0.2 μM) in agreement with published values. This validation, coupled with the compatibility of this platform with automation and parallelization, indicates significant potential for large-scale pharmaceutical ion channel screening.
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, CA 90095, USA.
authors.forename: Ahmad M
authors.initials: AM
authors.lastname: El-Arabi
authors.forename: Carl S
authors.initials: CS
authors.lastname: Salazar
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000737:chemistry / Q000378:metabolism; D055664:Electrochemical Techniques / Q000295:instrumentation / Q000379:methods*; D004566:Electrodes; D055724:Electrophysiological Phenomena; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry*; D008610:Menthol / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D050053:TRPM Cation Channels / Q000378:metabolism; D013696:Temperature
chemical_list: D001896:Boron Compounds; D007473:Ion Channels; D008051:Lipid Bilayers; D050053:TRPM Cation Channels; C498947:Trpm8 protein, rat; D008610:Menthol; C109986:2-aminoethoxydiphenyl borate