FIGURE 11.

Modulation of whole-cell Kv1.2 current by cPKA requires Ser-449. A–F, representative whole-cell currents due to wild-type (WT) and mutant Kv1.2 (S449A, S449D, S440A/S441A, and S440A/S441A/S449A) constructs evoked by 5-s voltage ramps from −80 to +40 mV (applied at 20-s intervals) immediately after membrane rupture (0 min) and after the indicated times of dialysis with control pipette solution (panel A; Kv1.2WT (WT (no cPKA)) or solution with cPKA (50 nm; B–F). The second tracing in each panel represents the stable level of current achieved after the indicated time. G, current density at +40 mV immediately after membrane rupture ±S.E. for untransfected HEK 293 cells (UT) and cells expressing Kv1.2-WT (WT (no cPKA) and WT), -S449A (S/A), -S449D (S/D), -S440A/S441A (A/A), or -S440A/S441A/S449A (A/A/A) mutant constructs used in A–F (numbers indicate n cells from >3 transfections). H, mean fractional change in current at +40 mV ± S.E. (evoked by the ramp protocol indicated in A) for cells expressing wild-type or mutant Kv1.2 constructs after dialysis with control pipette solution (WT (no cPKA)) or solution containing cPKA (Kv1.2-WT (WT), S449A (S/A), S449D (S/D), S440A/S441A (A/A), and S440A/S441A/S449A (A/A/A)) (n values are as in G). The asterisks indicate significantly different (p < 0.05) from Kv1.2-WT in the absence of PKA (i.e. WT (no cPKA)) determined by analysis of variance followed by the Bonferroni post-hoc test.