Kv1.1 Channelopathies: Pathophysiological Mechanisms and Therapeutic Approaches

Figures

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  Figure 1. Cartoon showing the localization of the Kv1.1 identified mutations associated with episodic ataxia type 1 and epilepsy. Dark blue circles, mutations associated with episodic ataxia; magenta circles, mutations associated with paroxysmal kinesigenic dyskinesia; yellow circles, mutations associated with hypomagnesemia; light blue circles, mutations showing ataxia and epilepsy; red stars, mutations associated with epilepsy without ataxia.

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  Figure 2. (A,B) Representative current traces evoked by 200 ms depolarizing steps (∆V +5 mV) from a holding potential of −80 mV to 40 mV, followed by a 150 ms step at −50 mV (inset) from Kv1.1WT and Kv1.1E283K channels expressed in HEK 293 cells (panels A and B, respectively). Kv1.1E283K channels activate more slowly than Kv1.1WT channels (τ at V1/2 is 5.2 ± 0.2 ms and 11.7 ± 0.6 ms, for WT and E283K channels, respectively), and produce smaller currents. (C) The current-voltage relationships for Kv1.1WT and Kv1.1E283K channels were obtained by plotting the normalized peak tail currents measured at -50 mV as a function of the pre-pulse potentials and fitting data points with a Boltzmann function (V1/2 is −25.8 ± 0.4 mV and −16.5 ± 0.3 mV, for WT and E283K channels, respectively; slope factor is 7.4 ± 0.4 mV and 7.8 ± 0.2 mV, for WT and E283K channels, respectively. (D) Homology model of the mutant Kv1.1E283K, built upon the Kv1.2 crystal structure (PDB code: 3LUT), showing the localization of the E283K mutation (red dots). A thorough characterization of Kv1.1E283K channels has been provided in [64].