Abbott GW .

	Figure 1. KChIP2b protects Kv4.3L from inhibition by PKC phosphorylation. (A) Sequence alignment (Clustal TCoffee) of the C-terminal end of human Kv4.2, Kv4.3L and Kv4.3S protein sequences, including the segment missing in Kv4.3S (underlined red) and the T504 PKC phosphorylation site (open box). *Conserved in all three sequences. Adapted from Abbott (2017). (B) Exemplar current traces recorded during +40 mV pulses (1 per minute) in the presence of 50 nM PMA, from Xenopus oocytes 36–56 h after injection of 1.5 ng cRNA encoding Kv4.3L or Kv4.3S, with (n = 7–12) or without (n = 6–7) 5 ng KChIP2b. Insets: center, color-coded key to traces; upper right, voltage clamp protocol. (C) Mean ± SEM normalized peak current magnitude at +40 mV during incubation in 50 nM PMA or normal bath solution (control) for Kv4.3 currents recorded in the absence of KChIP2b as in (B) (n = 6–7). ***P < 0.001 vs. other groups at 15 min. (D) Mean ± SEM normalized peak current magnitude at +40 mV during incubation in 50 nM PMA (unless indicated) for Kv4.3-KChIP2b currents recorded as in (B) (n = 7–12).
	Figure 2. KChIP2b does not prevent Kv4.3L threonine phosphorylation. (A) Western blot result showing hKv4.3L protein immunoblot (IB) with mouse monoclonal anti-Kv4.3 antibody, following immunoprecipitation (IP) with rabbit polyclonal anti-Kv4.3 antibody, 3 days after Kv4.3 cRNA injection in Xenopus oocytes, with or without co-injected KChIP2b cRNA. Oocytes were incubated for 30 min in 50 nM PMA prior to lysis. Representative of two independent experiments. (B) Western blot on similar samples as in (A) but using mouse monoclonal anti-phosphothreonine antibody for IB. Representative of two independent experiments.
	Figure 3. PKC stimulation has no effects on Kv4.3 and Kv4.3-KChIP2b inactivation rate and voltage dependence. (A) Inactivation rates at +40 mV (τ of single exponential fit) for oocytes expressing Kv4.3L and Kv4.3S alone or with KChIP2b, before and after 15 min incubation with 50 nM PMA (n = 6–12) or PDD (n = 3). Upper inset: voltage protocol. *P < 0.05. (B) Exemplar current trace recorded from a Xenopus oocyte expressing Kv4.3L-KChIP2b using the steady-state inactivation protocol (upper left inset). Zero current level indicated by dashed line. (C) Mean ± SEM fraction of available channels/voltage relationship for Kv4.3L vs. Kv4.3S, with/without 15 min pre-incubation in 50 nM PMA; currents recorded as in (B); n = 6–8. (D) Mean ± SEM fraction of available channels/voltage relationship for Kv4.3L-KChIP2b (n = 12–13) vs. Kv4.3S-KChIP2b (n = 5–9), with/without 15 min pre-incubation in 50 nM PMA; currents recorded as in (B).
	Figure 4. Kv4.3L T504 mutations alter inactivation rate and voltage dependence only with KChIP2b co-expression. (A) Exemplar current traces recorded at +40 mV from Xenopus oocytes expressing Kv4.3L (wild-type, T504A or T504D) or Kv4.3S, alone or with KChIP2b (voltage protocol inset). Zero current level indicated by dashed line. (B) Mean ± SEM peak currents at +40 mV for oocytes expressing Kv4.3 variants as in (A), in the absence of KChIP2b (n = 8–15). (C) Mean ± SEM peak currents at +40 mV for oocytes expressing Kv4.3 variants as in (A), with KChIP2b (n = 21–25). **P < 0.01 vs. other +KChIP2b groups. (D) Box plots showing individual and mean ± SEM values for τ of inactivation at +40 mV of T504A and T504D Kv4.3L, with (n = 34) vs. without (n = 17–21) KChIP2b, recorded as in (A). *P < 0.05. (E) Mean ± SEM fraction of available channels/voltage relationship for T504A and T504D Kv4.3L vs. Kv4.3S in the absence of KChIP2b (n = 10–13), using the steady-state inactivation protocol (inset). Curves for wild-type Kv4.3 subunits without KChIP2b (from Figure 3) included for comparison (blue lines as indicated). (F) Mean ± SEM fraction of available channels/voltage relationship for T504A and T504D Kv4.3L vs. Kv4.3S, with KChIP2b (n = 26–31), using the steady-state inactivation protocol as in (E). Curves for wild-type Kv4.3 subunits with KChIP2b (from Figure 3) included for comparison (red lines as indicated).
	Figure 5. KChIP2b regulates the effects of PKC stimulation on Kv4.3 inactivation recovery. (A) Exemplar current traces recorded using short (left) and long (right) inactivation recovery protocols (left inset), from a Xenopus oocyte expressing Kv4.3L and KChIP2b. (B) Mean ± SEM fractional current recovery plotted from traces recorded as in (A) for homomeric Kv4.3L or Kv4.3S in normal bath solution (control) or after 15 min in bath solution containing 50 nM PMA; n = 4–5. (C) Mean ± SEM fractional current recovery plotted from traces recorded as in (A) for Kv4.3L (n = 11–12) or Kv4.3S (n = 5–10) with KChIP2b in normal bath solution (control) or after 15 min in bath solution containing 50 nM PMA.
	Figure 6. KCNE2 restores the PKC sensitivity of Kv4.3L-KChIP2b activity. (A) Mean ± SEM normalized peak current magnitude at +40 mV (1 pulse per minute) during incubation in 50 nM PMA (n = 11–12) or normal bath solution (control; n = 5) for Kv4.3L with KCNE2. (B) Exemplar current traces recorded during +40 mV pulses (1 per minute) in the presence of 50 nM PMA, from Xenopus oocytes expressing encoding Kv4.3L with KCNE2 and KChIP2b. Insets: center, color-coded key to traces; lower left, voltage clamp protocol. (C) Mean ± SEM normalized peak current magnitude at +40 mV during incubation in 50 nM PMA (n = 8) or normal bath solution (control; n = 5) for cells as in (B).

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