title: Use-dependent activation of neuronal Kv1.2 channel complexes.
abstract: In excitable cells, ion channels are frequently challenged by repetitive stimuli, and their responses shape cellular behavior by regulating the duration and termination of bursts of action potentials. We have investigated the behavior of Shaker family voltage-gated potassium (Kv) channels subjected to repetitive stimuli, with a particular focus on Kv1.2. Genetic deletion of this subunit results in complete mortality within 2 weeks of birth in mice, highlighting a critical physiological role for Kv1.2. Kv1.2 channels exhibit a unique property described previously as "prepulse potentiation," in which activation by a depolarizing step facilitates activation in a subsequent pulse. In this study, we demonstrate that this property enables Kv1.2 channels to exhibit use-dependent activation during trains of very brief depolarizations. Also, Kv subunits usually assemble into heteromeric channels in the central nervous system, generating diversity of function and sensitivity to signaling mechanisms. We demonstrate that other Kv1 channel types do not exhibit use-dependent activation, but this property is conferred in heteromeric channel complexes containing even a single Kv1.2 subunit. This regulatory mechanism is observed in mammalian cell lines as well as primary cultures of hippocampal neurons. Our findings illustrate that use-dependent activation is a unique property of Kv1.2 that persists in heteromeric channel complexes and may influence function of hippocampal neurons.
authors.affiliation: Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, Canada, V6T 1Z3.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Baronas
authors.affiliation: Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, Canada, V6T 1Z3.
authors.forename: Brandon R
authors.initials: BR
authors.lastname: McGuinness
authors.affiliation: Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, Canada, V6T 1Z3.
authors.forename: G Stefano
authors.initials: GS
authors.lastname: Brigidi
authors.affiliation: Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, Canada, V6T 1Z3.
authors.forename: Rachel N
authors.initials: RN
authors.lastname: Gomm Kolisko
authors.affiliation: Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, Canada, V6T 1Z3.
authors.forename: Yury Y
authors.initials: YY
authors.lastname: Vilin
authors.affiliation: Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, Canada, V6T 1Z3.
authors.forename: Robin Y
authors.initials: RY
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, Canada, V6T 1Z3.
authors.forename: Francis C
authors.identifier: http://orcid.org/0000-0001-9318-1063
authors.initials: FC
authors.lastname: Lynn
authors.affiliation: Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, Canada, V6T 1Z3.
authors.forename: Shernaz X
authors.initials: SX
authors.lastname: Bamji
authors.affiliation: Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, Canada, V6T 1Z3.
authors.forename: Runying
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, Canada, V6T 1Z3 harley.kurata@ubc.ca.
authors.forename: Harley T
authors.initials: HT
authors.lastname: Kurata
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D006624:Hippocampus / Q000166:cytology; D015640:Ion Channel Gating; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051669:Shab Potassium Channels / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D051669:Shab Potassium Channels
keywords: Kv1.2; gating; modulation; potassium channel; signaling; use-dependence