Open AccessDeletion of neurturin impairs development of cholinergic nerves and heart rate control in postnatal mouse hearts
Author(s) -
Downs Anthony M.,
Jalloh Hawa B.,
Prater Kayla J.,
Fregoso Santiago P.,
Bond Cherie E.,
Hampton Thomas G.,
Hoover Donald B.
Publication year - 2016
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12779
Subject(s) - neurturin , cholinergic , endocrinology , medicine , carbachol , baroreflex , bradycardia , phenylephrine , chronotropic , autonomic nervous system , heart rate , glial cell line derived neurotrophic factor , neurotrophic factors , stimulation , blood pressure , receptor
The neurotrophic factor neurturin is required for normal cholinergic innervation of adult mouse heart and bradycardic responses to vagal stimulation. Our goals were to determine effects of neurturin deletion on development of cardiac chronotropic and dromotropic functions, vagal baroreflex response, and cholinergic nerve density in nodal regions of postnatal mice. Experiments were performed on postnatal C57 BL /6 wild‐type ( WT ) and neurturin knockout ( KO ) mice. Serial electrocardiograms were recorded noninvasively from conscious pups using an ECGenie apparatus. Mice were treated with atenolol to evaluate and block sympathetic effects on heart rate ( HR ) and phenylephrine ( PE ) to stimulate the baroreflex. Immunohistochemistry was used to label cholinergic nerves in paraffin sections. WT and KO mice showed similar age‐dependent increases in HR and decreases in PR interval between postnatal days (P) 2.5 and 21. Treatment with atenolol reduced HR significantly in WT and KO pups at P7.5. PE caused a reflex bradycardia that was significantly smaller in KO pups. Cholinergic nerve density was significantly less in nodal regions of P7.5 KO mice. We conclude that cholinergic nerves have minimal influence on developmental changes in HR and PR , QRS , and QT c intervals in mouse pups. However, cholinergic nerves mediate reflex bradycardia by 1 week postnatally. Deletion of neurturin impairs cholinergic innervation of the heart and the vagal efferent component of the baroreflex early during postnatal development.