title: Synthetic ion channel activity documented by electrophysiological methods in living cells.
abstract: Hydraphiles are synthetic ion channels that use crown ethers as entry portals and that span phospholipid bilayer membranes. Proton and sodium cation transport by these compounds has been demonstrated in liposomes and planar bilayers. In the present work, whole cell patch clamp experiments show that hydraphiles integrate into the membranes of human embryonic kidney (HEK 293) cells and significantly increase membrane conductance. The altered membrane permeability is reversible, and the cells under study remain vital during the experiment. Control compounds that are too short (C(8)-benzyl channel) to span the bilayer or are inactive owing to a deficiency in the central relay do not induce similar conductance increases. Control experiments confirm that the inactive channel analogues do not show nonspecific effects such as activation of native channels. These studies show that the combination of structural features that have been designed into the hydraphiles afford true, albeit simple, channel function in live cells.
authors.affiliation: Department of Chemistry, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8103, St. Louis, Missouri 63110, USA.
authors.forename: W Matthew
authors.initials: WM
authors.lastname: Leevy
authors.forename: James E
authors.initials: JE
authors.lastname: Huettner
authors.forename: Robert
authors.initials: R
authors.lastname: Pajewski
authors.forename: Paul H
authors.initials: PH
authors.lastname: Schlesinger
authors.forename: George W
authors.initials: GW
authors.lastname: Gokel
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D002463:Cell Membrane Permeability; D043844:Crown Ethers / Q000737:chemistry* / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D007668:Kidney / Q000166:cytology; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017470:Receptors, Glutamate / Q000737:chemistry / Q000378:metabolism
chemical_list: D043844:Crown Ethers; D007473:Ion Channels; D008051:Lipid Bilayers; D017470:Receptors, Glutamate; D007608:Kainic Acid