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. 2013 Aug;142(2):113–126. doi: 10.1085/jgp.201310996

Figure 4.

Figure 4.

Cholinergic regulation of pacemaker activity in WT and Girk4−/− SAN cells. (A) Examples of spontaneous action potentials recorded in SAN cells from WT and Girk4−/− hearts in control conditions (black traces) and after perfusion of ACh (gray traces) at the indicated doses. (B) Histograms of pacing rate of WT (closed bars) and Girk4−/− (open bars) SAN cells in control conditions (WT n = 6; Girk4−/− n = 6) and after perfusion of 0.003 (WT n = 5; Girk4−/− n = 7), 0.01 (WT n = 18; Girk4−/− n = 10), and 0.05 µM ACh (WT n = 5; Girk4−/− n = 7). (C) Dose–response relation of the percentage of slowing of pacemaker rate by ACh in WT (closed circles) and Girk4−/− (open circles) SAN cells. At 0.01 µM ACh, inactivation of Girk4 channels significantly reduced the negative chronotropic effect from 67% in WT to 26% in Girk4−/− SAN cells. At 0.05 µM ACh, pacing was absent in WT, whereas it was reduced to ∼50% in Girk4−/− SAN cells. Error bars represent SEM. Statistical symbols: **, P < 0.01; and ***, P < 0.001.