Figure 4. I262T alters Kvβ1.1-mediated voltage-dependent inactivation of Kv1.1 channels.
(A) (Left) Representative Kv1.1 current traces of WT, WT-I262T dimer, or I262T co-expressed with Kvβ1.1 (molar ratio 1:5) in Xenopus oocytes. The voltage protocol is the same as that in Fig. 1A. The external solution contains 3 mM KCl. (Right) I262T decelerates the fast inactivation kinetics of Kv1.1 channels. Inactivation time constants were derived from two-exponential fits of the falling phase of test currents. (B) I262T shifts the voltage-dependent inactivation of Kv1.1. (Left) Representative current traces in response to the voltage protocol comprising a 350-ms depolarizing prepulse potential (ranging from −80 mV to + 20 mV in + 5 mV steps), followed by a test pulse (fixed at + 60 mV) for 100 ms. (Right) Steady-state inactivation curves derived from the normalization of peak current amplitudes (at the + 60-mV test pulse; I/Imax) in response to different prepulse potentials. See Supplementary Table S1 for more details on the parameters of the inactivation curves. (C) Lack of effect of I262T on the inactivation recovery of Kv1.1. (Left) Representative current traces in response to a double-pulse voltage protocol comprising two consecutive 100-ms + 40-mV test pulses that were separated by −90- mV interpulses of increasing durations (from 0.05 to 9 sec). The dotted line denotes the recovery time course of the K+ current in response to the second test pulse. (Right) Normalized peak current amplitudes (at the second + 40-mV pulse) as a function of interpulse duration. (D) I262T changes the cumulative inactivation of Kv1.1. (Left) Representative current traces in response to a 40-Hz train of 3-ms + 40-mV test pulses with 25-ms interpulse intervals (holding at −90 mV). No –P/4 leak subtraction was performed. The dotted line denotes the time course of K+ current reduction in response to 15 consecutive test pulses. (Right) Normalized peak current amplitudes (at + 40 mV) as a function of test pulse number. See Supplementary Table S2 for more details on the kinetics of inactivation recovery and cumulative inactivation.