Involvement of hHCN4 serine 1157 in AMPK-mediated channel modulation. (A and B) In A and B, upper panels are typical current records, and lower panels are fully activated I/V relations, normalized to cell capacitance, from HEK293F cells in control conditions (black) and after AICAR treatment (red). Data from cells transfected with wild-type hHCN4 (left in A and B) are compared with data from cells transfected with S1157A or S1157D mutant channels (right in A and B, respectively). Linear fitting of I/V curves yielded the following normalized conductance values (nS/pF): (A) 1.06, 0.52 (left) and 1.04, 1.01 (right); (B) 1.02, 0.54 (left) and 1.08, 1.05 (right) for wild-type and AICAR-treated cells, respectively. In each experiment, control and mutant channels data are from the same day-matched transfection protocol. Statistical analysis and data comparisons are shown in Tables 1 and S2.