title: Mechanism of functional interaction between potassium channel Kv1.3 and sodium channel NavBeta1 subunit.
abstract: The voltage-gated potassium channel subfamily A member 3 (Kv1.3) dominantly expresses on T cells and neurons. Recently, the interaction between Kv1.3 and NavBeta1 subunits has been explored through ionic current measurements, but the molecular mechanism has not been elucidated yet. We explored the functional interaction between Kv1.3 and NavBeta1 through gating current measurements using the Cut-open Oocyte Voltage Clamp (COVC) technique. We showed that the N-terminal 1-52 sequence of hKv1.3 disrupts the channel expression on the Xenopus oocyte membrane, suggesting a potential role as regulator of hKv1.3 expression in neurons and lymphocytes. Our gating currents measurements showed that NavBeta1 interacts with the voltage sensing domain (VSD) of Kv1.3 through W172 in the transmembrane segment and modifies the gating operation. The comparison between G-V and Q-V with/without NavBeta1 indicates that NavBeta1 may strengthen the coupling between hKv1.3-VSD movement and pore opening, inducing the modification of kinetics in ionic activation and deactivation.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E. 57th street, Chicago, IL 60637, USA.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kubota
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E. 57th street, Chicago, IL 60637, USA.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Correa
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E. 57th street, Chicago, IL 60637, USA.
authors.forename: Francisco
authors.initials: F
authors.lastname: Bezanilla
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D051664:Kv1.3 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus / Q000378:metabolism
chemical_list: D051664:Kv1.3 Potassium Channel; D021122:Protein Subunits; D015222:Sodium Channels