title: Gating charge displacement in voltage-gated ion channels involves limited transmembrane movement.
abstract: Voltage-gated ion channels are responsible for generating electrical impulses in nerves and other excitable cells. The fourth transmembrane helix (S4) in voltage-gated channels is the primary voltage-sensing unit that mediates the response to a changing membrane electric field. The molecular mechanism of voltage sensing, particularly with respect to the magnitude of the transmembrane movement of S4, remains controversial. To determine the extent of this transmembrane movement, we use fluorescent resonance energy transfer between the S4 domain and a reference point in the lipid bilayer. The lipophilic ion dipicrylamine distributes on either side of the lipid bilayer depending on the membrane potential, and is used here as a resonance-energy-transfer acceptor from donor molecules attached to several positions in the Shaker K+ channel. A voltage-driven transmembrane movement of the donor should produce a transient fluorescence change because the acceptor also translocates as a function of voltage. In Shaker K+ channels no such transient fluorescence is observed, indicating that the S4 segment does not translocate across the lipid bilayer. Based on these observations, we propose a molecular model of voltage gating that can account for the observed 13e gating charge with limited transmembrane S4 movement.
authors.affiliation: Departments of Physiology and Anesthesiology, David Geffen School of Medicine, UCLA, 650 Charles E. Young Dr. South, Los Angeles, California 90025, USA.
authors.forename: Baron
authors.initials: B
authors.lastname: Chanda
authors.forename: Osei Kwame
authors.initials: OK
authors.lastname: Asamoah
authors.forename: Rikard
authors.initials: R
authors.lastname: Blunck
authors.forename: Benoît
authors.initials: B
authors.lastname: Roux
authors.forename: Francisco
authors.initials: F
authors.lastname: Bezanilla
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D015640:Ion Channel Gating; D008051:Lipid Bilayers / Q000378:metabolism; D008564:Membrane Potentials; D008958:Models, Molecular; D015335:Molecular Probes; D009068:Movement; D010851:Picrates; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D051637:Shaker Superfamily of Potassium Channels
chemical_list: D008051:Lipid Bilayers; D015335:Molecular Probes; D010851:Picrates; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051637:Shaker Superfamily of Potassium Channels; C011454:dipicrylamine