title: Connexin40 imparts conduction heterogeneity to atrial tissue.
abstract: Impulse propagation in cardiac tissue is a complex process in which intercellular coupling through gap junction channels is a critical component. Connexin40 (Cx40) is an abundant gap junction protein that is expressed in atrial myocytes. Alterations in the expression of Cx40 have been implicated in atrial arrhythmogenesis. The purpose of the current study was to assess the role of Cx40 in atrial impulse propagation. High-resolution optical mapping was used to study conduction in the right and left atrial appendages of isolated Langendorff-perfused murine hearts. Wild-type (Cx40(+/+)), heterozygous (Cx40(+/-)), and knockout (Cx40(-/-)) mice, both adult and embryonic, were studied to assess the effects of reduced Cx40 expression on sinus node function and conduction velocity at different pacing cycle lengths (100 and 60 ms). In both adult and late-stage embryonic Cx40(+/+) mice, heterogeneity in CV was found between the right and left atrial appendages. Either partial (Cx40(+/-)) or complete (Cx40(-/-)) deletion of Cx40 was associated with the loss of conduction heterogeneity in both adult and embryonic mice. Additionally, sinus node impulse initiation was found to be ectopic in Cx40(-/-) mice at 15.5 days postcoitus, whereas Cx40(+/+) mice showed normal activation occurring near the crista terminalis. Our findings suggest that Cx40 plays an essential role in establishing interatrial conduction velocity heterogeneity in the murine model. Additionally, we describe for the first time a developmental requirement for Cx40 in normal sinus node impulse initiation at 15.5 days postcoitus.
authors.affiliation: Leon H Charney Division of Cardiology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Leaf
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Feig
authors.forename: Carolina
authors.initials: C
authors.lastname: Vasquez
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Riva
authors.forename: Cindy
authors.initials: C
authors.lastname: Yu
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Lader
authors.forename: Andrianos
authors.initials: A
authors.lastname: Kontogeorgis
authors.forename: Elvera L
authors.initials: EL
authors.lastname: Baron
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Peters
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fisher
authors.forename: David E
authors.initials: DE
authors.lastname: Gutstein
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Morley
mesh_terms: D000200:Action Potentials; D000367:Age Factors; D000375:Aging / Q000378:metabolism; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D020517:Atrial Appendage / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004562:Electrocardiography; D006321:Heart / Q000196:embryology; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012849:Sinoatrial Node / Q000196:embryology / Q000378:metabolism*; D000097003:Gap Junction alpha-5 Protein
chemical_list: D018031:Connexin 43; D017630:Connexins; D012333:RNA, Messenger; D000097003:Gap Junction alpha-5 Protein