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Structural and functional cardiac cholinergic deficits in adult neurturin knockout mice
Author(s) -
Mabe Abigail M.,
Hoover Donald B.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1230.9
Subject(s) - neurturin , cholinergic , cholinergic fibers , medicine , endocrinology , cholinergic neuron , vesicular acetylcholine transporter , knockout mouse , carbachol , acetylcholine , choline acetyltransferase , stimulation , neurotrophic factors , glial cell line derived neurotrophic factor , receptor
Neurturin (NRTN) is a neurotrophic factor required during development for normal cholinergic innervation of the mouse heart. This study used NRTN knockout (KO) and wild type (WT) mice to determine the impact of NRTN deletion on adult intracardiac cholinergic neurons and nerve fibers and on cardiac cholinergic function. Immunohistochemical analysis of atrial tissue stained for vesicular ACh transporter revealed that sinoatrial node cholinergic nerve density was reduced by more than 40% in 8 week KO hearts. Additionally, the number of cholinergic neurons in KO hearts was 80% less than in WT, and KO neurons were 22% smaller in size. Atrial ACh levels were significantly lower in 16 week KO mice compared to WT (1.8±0.3 vs 3.7±0.8 pmol/mg wt; P<0.02), as expected from cholinergic neuron and nerve fiber deficits. Maximum heart rate (HR) responses to right vagal nerve stimulation (VNS) were decreased in 16 week KO (38±6 vs 81±3% decrease at 20Hz; P<0.0001), with no difference in baseline HR. KO animals took longer to reach maximum bradycardia during VNS and longer to recover to baseline HR upon stimulus termination. Data from isolated atrial preparations showed no change in postjunctional cholinergic sensitivity. These results demonstrate that NRTN KO leads to structural and functional cholinergic deficits in the heart but residual cholinergic nerve fibers retain ability to modify cardiac function. Supported by the AHA SE Affiliate.