A regulatory site in the distal C terminus of HCN4 is required for PKA modulation. Representative whole-cell current traces (insets) and average conductance–voltage plots for wild-type HCN4 (A), HCN4-ΔNΔC (B), HCN4-ΔC (C), HCN4-Nx4 (D), HCN4-Δ1012 (E), and HCN4-Cx4 (F) expressed in CHO cells. Black lines and closed circles indicate control intracellular solution; red lines and open circles indicate PKA-containing intracellular solution. Currents were elicited by 3-s hyperpolarizing voltage steps ranging from −40 to −180 mV in 10-mV increments (as indicated). Scale bars: (A, B, and E, insets) 500 pA, 500 ms; (C, D, and F, insets) 1 nA, 500 ms. Cartoons in each panel depict the constructs, where red and green circles indicate confirmed and unconfirmed PKA sites, and open circles indicate alanine substitutions of PKA sites.