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Rate-limiting Reactions Determining Different Activation Kinetics of Kv1.2and Kv2.1 Channels
Authors:A?Scholle  S?Dugarmaa  T?Zimmer  M?Leonhardt  R?Koopmann  B?Engeland  O?Pongs  Email author" target="_blank">K?BenndorfEmail author
Institution:(1) Institut für Physiologie, Herz-Kreislauf-Physiologie, Friedrich-Schiller-Universität, 07740 Jena, Germany;(2) Zentrum für Molekulare Neurobiologie, Institut für Neurale Signalverarbeitung, UKE (Haus 42), Martinistr. 52, 20251 Hamburg, Germany
Abstract:To identify the mechanisms underlying the faster activation kinetics in Kv1.2 channels compared to Kv2.1 channels, ionic and gating currents were studied in rat Kv1.2 and human Kv2.1 channels heterologously expressed in mammalian cells. At all voltages the time course of the ionic currents could be described by an initial sigmoidal and a subsequent exponential component and both components were faster in Kv1.2 than in Kv2.1 channels. In Kv1.2 channels, the activation time course was more sigmoid at more depolarized potentials, whereas in Kv2.1 channels it was somewhat less sigmoid at more depolarized potentials. In contrast to the ionic currents, the ON gating currents were similarly fast for both channels. The main portion of the measured ON gating charge moved before the ionic currents were activated. The equivalent gating charge of Kv1.2 ionic currents was twice that of Kv2.1 ionic currents, whereas that of Kv1.2 ON gating currents was smaller than that of Kv2.1 ON gating currents. In conclusion, the different activation kinetics of Kv1.2 and Kv2.1 channels are caused by rate-limiting reactions that follow the charge movement recorded from the gating currents. In Kv1.2 channels, the reaction coupling the voltage-sensor movement to the pore opening contributes to rate limitation in a voltage-dependent fashion, whereas in Kv2.1 channels, activation is additionally rate-limited by a slow reaction in the subunit gating.
Keywords:Kv2  1 and Kv1  2 channels  Equivalent gating charge  Ionic and gating current  Activation time course  Voltage dependence
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