title: Kv3.1 uses a timely resurgent K(+) current to secure action potential repolarization.
abstract: High-frequency action potential (AP) transmission is essential for rapid information processing in the central nervous system. Voltage-dependent Kv3 channels play an important role in this process thanks to their high activation threshold and fast closure kinetics, which reduce the neuron's refractory period. However, premature Kv3 channel closure leads to incomplete membrane repolarization, preventing sustainable AP propagation. Here, we demonstrate that Kv3.1b channels solve this problem by producing resurgent K(+) currents during repolarization, thus ensuring enough repolarizing power to terminate each AP. Unlike previously described resurgent Na(+) and K(+) currents, Kv3.1b's resurgent current does not originate from recovery of channel block or inactivation but results from a unique combination of steep voltage-dependent gating kinetics and ultra-fast voltage-sensor relaxation. These distinct properties are readily transferrable onto an orthologue Kv channel by transplanting the voltage-sensor's S3-S4 loop, providing molecular insights into the mechanism by which Kv3 channels contribute to high-frequency AP transmission.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, GCIS Building, Room W244, 929 East 57th Street, Chicago, Illinois 60637, USA.|Department of Biomedical Sciences, University of Antwerp, Antwerp 2610, Belgium.
authors.forename: Alain J
authors.initials: AJ
authors.lastname: Labro
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, GCIS Building, Room W244, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Priest
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, GCIS Building, Room W244, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Jérôme J
authors.initials: JJ
authors.lastname: Lacroix
authors.affiliation: Department of Biomedical Sciences, University of Antwerp, Antwerp 2610, Belgium.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Snyders
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, GCIS Building, Room W244, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Francisco
authors.initials: F
authors.lastname: Bezanilla
mesh_terms: D000200:Action Potentials / Q000235:genetics*; D000818:Animals; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008390:Markov Chains; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons; D009865:Oocytes / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D051670:Shaw Potassium Channels / Q000235:genetics* / Q000378:metabolism; D014981:Xenopus
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; C489597:KCNC1 protein, human; C121382:KCNH4 protein, human; D009419:Nerve Tissue Proteins; D051670:Shaw Potassium Channels; D011188:Potassium