Age dependence of AMPK action of I _f in pacemaker cells. (A–D) Whole-cell recordings of I_f in 3-mo-old (young) (A and B) and 24-mo-old (old) (C and D) mouse SAN cells in control (black) and after 4-h treatment with AMPK activator (AICAR 1 mM) (red). Data are obtained from N = 3 young and N = 4 old mice. (A and C) Representative current traces (left) and activation curves (right). Best fitting yielded the following values (mV): (A) V1/2 = −89.9 ± 0.81 (n = 21) and −87.8 ± 0.88 (n = 18) (n.s.); s = 8.0 ± 0.4 and 7.4 ± 0.3, for controls and AICAR-treated cells, respectively; (C) V1/2 = −89.5 ± 0.78 (n = 23) and −90.3 ± 0.97 (n = 15) (n.s.); s = 8.0 ± 0.4 and 8.5 ± 0.7 for control and AICAR-treated cells, respectively. (B and D) I/V relations; bar graphs on the left show the distributions of current densities at −125 mV. Mean ± SEM values were (pA/pF) as follows: (B) −42.8 ± 5.34 (n = 21) and −27.9 ± 3.48 (n = 21) (P = 0.0037, **); (D) −25.4 ± 2.91 (n = 23) and −26.5 ± 3.37 (n = 16) (P = 0.9894, n.s.), for control and AICAR-treated cells, respectively. The difference between current densities from old and young mice in control conditions was significant (P = 0.0112, *). Details of statistical analysis are shown in Table S1.