Voltage-dependent K+ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane.
Voltage-dependent K(+) (Kv) channels underlie action potentials through gating conformational changes that are driven by membrane voltage. In this study of the paddle chimera Kv channel, we demonstrate that the rate of channel opening, the voltage dependence of the open probability, and the maximum achievable open probability depend on the lipid membrane environment. The activity of the voltage sensor toxin VsTx1, which interferes with voltage-dependent gating by partitioning into the membrane and binding to the channel, also depends on the membrane. Membrane environmental factors that influence channel function are divisible into two general categories: lipid compositional and mechanical state. The mechanical state can have a surprisingly large effect on the function of a voltage-dependent K(+) channel, including its pharmacological interaction with voltage sensor toxins. The dependence of VSTx1 activity on the mechanical state of the membrane leads us to hypothesize that voltage sensor toxins exert their effect by perturbing the interaction forces that exist between the channel and the membrane.
Schmidt
Daniel
D
Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
MacKinnon
Roderick
R
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology*; D008051:Lipid Bilayers / Q000378:metabolism*; D008954:Models, Biological; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013111:Spider Venoms / Q000494:pharmacology*; D013314:Stress, Mechanical; D013396:Suction; D014982:Xenopus laevis
D008051:Lipid Bilayers; D010455:Peptides; D024642:Potassium Channels, Voltage-Gated; D011993:Recombinant Fusion Proteins; D013111:Spider Venoms; C487989:VSTX1 protein, Grammostola spatulata