Figure 2. The effects of the Rgs6 on HRV are mediated by the I_KACh and are influenced by the m₂R activity.

A, Schematic representation of the pathway targeted both genetically and pharmacologically. Abbreviations are: atropine (Atro), carbamylcholine (CCh). B, Effect of m₂R blockade by atropine on HRV in wild-type (black; n = 7) and Rgs6^−/− hearts (red; n = 10). No significant effect of drug was observed in wild-type hearts. C, Increased sensitivity of Rgs6^−/− hearts to m₂R stimulation and its rescue by I_KACh (Girk4) ablation. Increasing concentrations of CCh were applied to isolated perfused hearts (n = 4–6 per genotype). D, m₂R stimulation non-proportionately increased HRV in Rgs6^−/− hearts. Hearts (n = 3–6 per genotype) were perfused with CCh (∼IC₁₀ concentration) identified from dose-response studies, followed by measurement of changes in the RMSSD parameters. Symbols: * P<0.05 vs wild-type, #P<0.05 vs treatment.