Cardiac sympathetic nerve transdifferentiation reduces action potential heterogeneity after myocardial infarction
| العنوان: | Cardiac sympathetic nerve transdifferentiation reduces action potential heterogeneity after myocardial infarction |
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| المؤلفون: | Beth A. Habecker, Srinivas Tapa, William R. Woodward, Crystal M. Ripplinger, Lianguo Wang, Antoinette Olivas, Matthew R. Blake, Samantha D. Francis Stuart |
| المصدر: | Am J Physiol Heart Circ Physiol |
| بيانات النشر: | American Physiological Society, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Adrenergic Neurons, medicine.medical_specialty, Sympathetic Nervous System, Physiology, Myocardial Infarction, Action Potentials, Calcium in biology, Choline O-Acetyltransferase, Mice, Norepinephrine, Physiology (medical), Internal medicine, medicine, Animals, Calcium Signaling, Myocardial infarction, Mice, Knockout, business.industry, Transdifferentiation, Heart, medicine.disease, Cholinergic Neurons, Disease Models, Animal, Electrophysiology, Endocrinology, Cardiac sympathetic nerve, Cell Transdifferentiation, Cholinergic, Cardiology and Cardiovascular Medicine, business, Acetylcholine, Research Article, medicine.drug |
| الوصف: | 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. |
| تدمد: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00412.2019 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7fe46ca0654425763a7a81e83d4c0617 https://doi.org/10.1152/ajpheart.00412.2019 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7fe46ca0654425763a7a81e83d4c0617 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221539 03636135 |
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| DOI: | 10.1152/ajpheart.00412.2019 |