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. 2017 Jan 27;8:14155. doi: 10.1038/ncomms14155

Figure 3. Atrial cholinergic modulation alters ventricular cAMP levels.

Figure 3

(a) Cyclic adenosine monophosphate (cAMP) biosensor fluorescence in yellow (YFP) and cyan (CFP) channels during FRET measurements in a Langendorff-perfused heart. The red/blue squares at the ventricle/atrium indicate the areas of measurement. (b) Representative experiment depicting time-resolved cAMP dynamics (presented as normalized CFP/YFP ratio) during perfusion with isoproterenol (ISO, 1 × 10−7 M) and targeted atrial application of nicotine (6.2 × 10−6 M). cAMP levels in the left atrium and ventricle were decreased by nicotine. (c) Relative changes in cAMP levels (% of ISO response) in atria and ventricles during local atrial application of nicotine in control hearts without pharmacological intervention (n=8), after partial atrial denervation (PAD; n=5) and during ganglionic (hexamethonium, 5 × 10−4 M; n=5) or muscarinergic blockade (atropine, 1 × 10−5 M; n=5) are depicted. In the atrium, targeted atrial nicotine application reduced relative atrial cAMP levels in controls and PAD hearts. This effect was reduced after ganglionic blockade (n=5; P=0.009; unpaired t-test) or muscarinergic blockade (n=5; P=0.011; Mann–Whitney test). In the ventricle, relative changes in cAMP levels during targeted atrial application of nicotine was obvious in controls (n=8) but abolished in PAD hearts (n=5; P=0.018; unpaired t-test) and during ganglionic (n=5; P=0.023; unpaired t-test) or muscarinergic blockade (n=5; P=0.036; unpaired t-test), indicating an inhibition of parasympathetic activity. (d) After stimulation with the water-soluble forskolin analogue NKH477 (1 × 10−5 M; n=5), relative changes in cAMP levels (% of NKH477 response) during local atrial application of nicotine in control hearts were recorded for the atrium and ventricle. Muscarinergic blockade applied in the same hearts reduced cAMP levels in the atrium (P=0.019; paired t-test) and ventricle (P=0.039; paired t-test) of NKH477 stimulated hearts. All the values shown are mean±s.e.m. *P<0.05, **P<0.01.