Cardiac sympathetic nerves undergo
cholinergic transdifferentiation following reperfused
myocardial infarction (MI), whereby the sympathetic nerves release both
norepinephrine (NE) and
acetylcholine (ACh). The functional electrophysiological consequences of post-MI transdifferentiation have never been explored. We performed MI or
sham surgery in wild-type (WT) mice and mice in which
choline acetyltransferase was deleted from adult noradrenergic neurons [knockout (KO)]. Electrophysiological activity was assessed with optical mapping of action potentials (AP) and intracellular Ca2+ transients (CaT) in innervated Langendorff-perfused hearts. KO MI hearts had similar NE content but reduced ACh content compared with WT MI hearts (0.360 ± 0.074 vs. 0.493 ± 0.087 pmol/mg; KO, n = 6; WT, n = 4; P < 0.05). KO MI hearts also had higher basal ex vivo heart rates versus WT MI hearts (328.5 ± 35.3 vs. 247.4 ± 62.4 beats/min; KO, n = 8; WT, n = 6; P < 0.05). AP duration at 80% repolarization was significantly shorter in the remote and border zones of KO MI versus WT MI hearts, whereas AP durations (APDs) were similar in
infarct regions. This APD heterogeneity resulted in increased APD dispersion in the KO MI versus WT MI hearts (11.9 ± 2.7 vs. 8.2 ± 2.3 ms; KO, n = 8; WT, n = 6; P < 0.05), which was eliminated with
atropine. CaT duration at 80% and CaT alternans magnitude were similar between groups both with and without sympathetic nerve stimulation. These results indicate that
cholinergic transdifferentiation following MI prolongs APD in the remote and border zone and reduces APD heterogeneity.NEW & NOTEWORTHY Cardiac sympathetic neurons undergo
cholinergic transdifferentiation following
myocardial infarction; however, the electrophysiological effects of corelease of
norepinephrine and
acetylcholine (ACh) have never been assessed. Using a mouse model in which
choline acetyltransferase was deleted from adult noradrenergic neurons and optical mapping of innervated hearts, we found that corelease of ACh reduces dispersion of action potential duration, which may be antiarrhythmic.