Sympathetic and parasympathetic control of the heart is a classic example of @entity1063 (NE) and @entity934 ( @entity3451 ) triggering opposing actions. Sympathetic NE increases heart rate and contractility through activation of b receptors, whereas parasympathetic @entity3451 slows the heart through muscarinic receptors. Sympathetic neurons can undergo a developmental transition from production of NE to @entity3451 and we provide evidence that @entity19 cardiac sympathetic nerves transiently produce @entity3451 after @entity583 ( @entity583 ). @entity3451 levels increased in viable heart tissue 10-14 d after @entity583 , returning to control levels at 21 d, whereas NE levels were stable. At the same time, the genes required for @entity3451 synthesis increased in stellate ganglia, which contain most of the sympathetic neurons projecting to the heart. Immunohistochemistry 14 d after @entity583 revealed @entity1877 acetyltransferase ( @entity4268 ) in stellate sympathetic neurons and vesicular @entity3451 transporter immunoreactivity in @entity4149 hydroxylase-positive cardiac sympathetic fibers. Finally, selective deletion of the @entity4268 gene from adult sympathetic neurons prevented the @entity1188 -induced increase in cardiac @entity3451 . Deletion of the @entity37165 cytokine receptor from sympathetic neurons prevented the induction of cholinergic genes after @entity583 , suggesting that inflammatory cytokines induce the transient acquisition of a cholinergic phenotype in cardiac sympathetic neurons. Ex vivo experiments examining the effect of NE and @entity3451 on @entity95 cardiac action potential duration revealed that @entity3451 blunted both the NE-stimulated decrease in cardiac action potential duration and increase in myocyte @entity460 transients. This raises the possibility that sympathetic co-release of @entity3451 and NE may impair adaptation to high heart rates and increase @entity943 susceptibility. SIGNIFICANCE STATEMENT: Sympathetic neurons normally make @entity1063 (NE), which increases heart rate and the contractility of cardiac myocytes. We found that, after @entity583 , the sympathetic neurons innervating the heart begin to make @entity934 ( @entity3451 ), which slows heart rate and decreases contractility. Several lines of evidence confirmed that the source of @entity3451 was sympathetic nerves rather than parasympathetic nerves that are the normal source of @entity3451 in the heart. Global application of NE with or without @entity3451 to ex vivo hearts showed that @entity3451 partially reversed the NE-stimulated decrease in cardiac action potential duration and increase in myocyte @entity460 transients. That suggests that sympathetic co-release of @entity3451 and NE may impair adaptation to high heart rates and increase @entity943 susceptibility.

XXXX Causes Transient Cholinergic Transdifferentiation of Cardiac Sympathetic Nerves via @entity37165 .

@entity943 :: ('MESH:D001145', 'Disease') :: ['arrhythmia'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity4268 :: ('8063', 'Species') :: ['ChAT'] @entity95 :: ('9986', 'Species') :: ['rabbit'] @entity37165 :: ('MESH:C005759', 'Chemical') :: ['gp130'] @entity1877 :: ('MESH:D002794', 'Chemical') :: ['choline'] @entity1188 :: ('MESH:D007238', 'Disease') :: ['infarction'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity3451 :: ('D000109', 'Chemical') :: ['ACh'] @entity583 :: ('MESH:D009203', 'Disease') :: ['myocardial infarction', 'MI'] @entity1063 :: ('MESH:D009638', 'Chemical') :: ['norepinephrine'] @entity4149 :: ('D014443', 'Chemical') :: ['tyrosine'] @entity934 :: ('MESH:D000109', 'Chemical') :: ['acetylcholine']
@entity583 :: (MESH:D009203,Disease) :: ['Myocardial Infarction']
