title: Molecular and electrical characterization of the canine cardiac ventricular septum.
abstract: Electrophysiological heterogeneity in the ventricular septum (VS) has been poorly addressed. In this study we investigated the electrophysiological and molecular composition of the VS in control sinus rhythm (SR) and chronic, complete atrio-ventricular block (CAVB) dogs. In the latter model, we anticipated that the increased inter-ventricular differences in action potential duration (APD; LV >RV) would accentuate the intrinsic heterogeneous composition of the VS. Steady-state mRNA levels of 10 important cardiac ion channels subunits as well as action potential (AP) characteristics (APD95, phase 1 amplitude (P1A), resting membrane potential) were measured in both sides of the VS excluding a small mid-myocardial strip (right: RVS, left: LVS). In SR, differences in steady-state mRNA between the two septal layers were observed for KChIP2 (approximately fivefold, P <0.01) and KCNQ1 (approximately twofold, P <0.05) with significantly higher levels of steady-state mRNA in the RVS compared to LVS. Correspondingly, shorter APDs and lower P1As (more spike and dome) were found in RVS, although the AP differences were subtle. This transseptal expression of KChIP2 and KCNQ1 corresponded with the observed differential expression levels in the right ventricle (RV) and left ventricular (LV) free wall, respectively. Electrical remodeling due to CAVB was also observed in the VS as was shown by approximately twofold lower levels in KCND3, KCNH2 and KCNQ1 mRNA (P <0.05) in the LVS compared to SR, thereby creating new or eliminating existing transseptal gradients. In parallel to changes in steady-state mRNA, CAVB resulted in a loss of the spike and dome morphology and longer APD95 (P <0.05) in the LVS. It is concluded that similar to other regions in the cardiac ventricles, the canine VS is molecularly and electrically heterogeneous. In the CAVB dog, this septal heterogeneity becomes accentuated as a result of electrical remodeling.
authors.affiliation: Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Christian
authors.initials: C
authors.lastname: Ramakers
authors.forename: Milan
authors.initials: M
authors.lastname: Stengl
authors.forename: Roel L H M G
authors.initials: RL
authors.lastname: Spätjens
authors.forename: Antoon F M
authors.initials: AF
authors.lastname: Moorman
authors.forename: Marc A
authors.initials: MA
authors.lastname: Vos
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics; D004285:Dogs; D004594:Electrophysiology; D006346:Heart Septum / Q000502:physiology*; D006352:Heart Ventricles / Q000033:anatomy & histology; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D051605:Kv Channel-Interacting Proteins; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D016276:Ventricular Function
chemical_list: D002135:Calcium-Binding Proteins; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D051605:Kv Channel-Interacting Proteins; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger