Effects of HCN4 knockout on spontaneous activity of single SAN cells. (A) Sample action potentials recorded from SAN cells isolated from control mice before and at day 5 (Upper panels) and from ciHCN4-KO mice at day 2 and day 5 of Tam treatment. Rates from 2- to 4-s-long recordings were 434.4, 436.4, 288.1, and 170.4 bpm, respectively. (B) Mean rates from cells of the same mouse categories as in A plotted against the time of recording. Control rates were 444.5 ± 23.7 bpm (untreated, n = 15/8 cells/mice) and 422.0 ± 24.5 bpm (5-d exposure to Tam or vehicle, n = 12/6 cells/mice); ciHCN4-KO rates were 293.6 ± 20.2 bpm (day 2, n = 20/6 cells/mice) and 173.1 ± 21.6 bpm (day 5, n = 26/9 cells/mice). All values were significantly different from each other (P < 0.05) except control vs. control day 5. The y axis on the right represents normalized values. The time courses of mean normalized telemetric heart rate of control and ciHCN4-KO mice from Fig. 2B are also plotted for comparison.