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Progress in Biophysics and Molecular... 2008Cardiac pacemaking in the sinoatrial (SA) node and atrioventricular (AV) node is generated by an interplay of many ionic currents, one of which is the funny pacemaker... (Comparative Study)
Comparative Study Review
Cardiac pacemaking in the sinoatrial (SA) node and atrioventricular (AV) node is generated by an interplay of many ionic currents, one of which is the funny pacemaker current (If). To understand the functional role of If in two different pacemakers, comparative studies of spontaneous activity and expression of the HCN channel in mouse SA node and AV node were performed. The intrinsic cycle length (CL) is 179+/-2.7 ms (n=5) in SA node and 258+/-18.7 ms (n=5) in AV node. Blocking of If current by 1 micromol/L ZD7288 increased the CL to 258+/-18.7 ms (n=5) and 447+/-92.4 ms (n=5) in SA node and AV node, respectively. However, the major HCN channel, HCN4 expressed at low level in the AV node compared to the SA node. To clarify the discrepancy between the functional importance of If and expression level of HCN4 channel, a SA node cell model was used. Increasing the If conductance resulted in decreasing in the CL in the model, which explains the high pacemaking rate and high expression of HCN channel in the SA node. Resistance to the blocking of If in the SA node might result from compensating effects from other currents (especially voltage sensitive currents) involved in pacemaking. The computer simulation shows that the difference in the intrinsic CL could explain the difference in response to If blocking in these two cardiac nodes.
Topics: Action Potentials; Animals; Atrioventricular Node; Biological Clocks; Humans; Sinoatrial Node
PubMed: 17905415
DOI: 10.1016/j.pbiomolbio.2007.07.009 -
Journal of Molecular and Cellular... Aug 2016Background inward sodium current (IB,Na) that influences cardiac pacemaking has been comparatively under-investigated. The aim of this study was to determine for the...
Background inward sodium current (IB,Na) that influences cardiac pacemaking has been comparatively under-investigated. The aim of this study was to determine for the first time the properties and role of IB,Na in cells from the heart's secondary pacemaker, the atrioventricular node (AVN). Myocytes were isolated from the AVN of adult male rabbits and mice using mechanical and enzymatic dispersion. Background current was measured using whole-cell patch clamp and monovalent ion substitution with major voltage- and time-dependent conductances inhibited. In the absence of a selective pharmacological inhibitor of IB,Na, computer modelling was used to assess the physiological contribution of IB,Na. Net background current during voltage ramps was linear, reversing close to 0mV. Switching between Tris- and Na(+)-containing extracellular solution in rabbit and mouse AVN cells revealed an inward IB,Na, with an increase in slope conductance in rabbit cells at -50mV from 0.54±0.03 to 0.91±0.05nS (mean±SEM; n=61 cells). IB,Na magnitude varied in proportion to [Na(+)]o. Other monovalent cations could substitute for Na(+) (Rb(+)>K(+)>Cs(+)>Na(+)>Li(+)). The single-channel conductance with Na(+) as charge carrier estimated from noise-analysis was 3.2±1.2pS (n=6). Ni(2+) (10mM), Gd(3+) (100μM), ruthenium red (100μM), or amiloride (1mM) produced modest reductions in IB,Na. Flufenamic acid was without significant effect, whilst La(3+) (100μM) or extracellular acidosis (pH6.3) inhibited the current by >60%. Under the conditions of our AVN cell simulations, removal of IB,Na arrested spontaneous activity and, in a simulated 1D-strand, reduced conduction velocity by ~20%. IB,Na is carried by distinct low conductance monovalent non-selective cation channels and can influence AVN spontaneous activity and conduction.
Topics: Action Potentials; Algorithms; Animals; Atrioventricular Node; Computer Simulation; Electrophysiological Phenomena; Male; Mice; Models, Cardiovascular; Myocardium; Patch-Clamp Techniques; Rabbits; Sodium
PubMed: 27132017
DOI: 10.1016/j.yjmcc.2016.04.014 -
British Heart Journal Aug 1975The atrio-His bundle tracts are very rare; only two have been found in 687 hearts studied histologically. These tracts have a similar appearance to those of the...
The atrio-His bundle tracts are very rare; only two have been found in 687 hearts studied histologically. These tracts have a similar appearance to those of the atrioventricular bundle and form a complete bypass of the atrioventricular node. In their presence the electrocardiogram may show a short or normal PR interval. They may be responsible for some cases of very rapid ventricular response to supraventricular arrhythmias.
Topics: Atrioventricular Node; Bundle of His; Heart Atria; Heart Conduction System; Humans; Middle Aged
PubMed: 1191446
DOI: 10.1136/hrt.37.8.853 -
The Anatomical Record. Part A,... Oct 2004In the normal heart, the atrioventricular node (AVN) is part of the sole pathway between the atria and ventricles. Under normal physiological conditions, the AVN... (Review)
Review
In the normal heart, the atrioventricular node (AVN) is part of the sole pathway between the atria and ventricles. Under normal physiological conditions, the AVN controls appropriate frequency-dependent delay of contractions. The AVN also plays an important role in pathology: it protects ventricles during atrial tachyarrhythmia, and during sinoatrial node failure an AV junctional pacemaker can drive the heart. Finally, the AV junction provides an anatomical substrate for reentry. Using fluorescent imaging with voltage-sensitive dyes and immunohistochemistry, we have investigated the structure-function relationship of the AV junction during normal conduction, reentry, and junctional rhythm. We identified molecular and structural heterogeneity that provides a substrate for the dual-pathway AVN conduction. We observed heterogeneity of expression of three isoforms of connexins: Cx43, Cx45, and Cx40. We identified the site of origin of junctional rhythm at the posterior extension of the AV node in 79% (n = 14) of the studied hearts. This structure was similar to the compact AV node as determined by morphologic and molecular investigations. In particular, both the posterior extension and the compact node express the pacemaking channel HCN4 (responsible for the I(F) current) and neurofilament 160. In the rabbit heart, AV junction conduction, reentrant arrhythmia, and spontaneous rhythm are governed by heterogeneity of expression of several isoforms of gap junctions and ion channels. Uniform neurofilament expression suggests that AV nodal posterior extensions are an integral part of the cardiac pacemaking and conduction system. On the other hand, differential expression of Cx isoforms in this region provides an explanation of longitudinal dissociation, dual-pathway electrophysiology, and AV nodal reentrant arrhythmogenesis.
Topics: Animals; Arrhythmias, Cardiac; Atrioventricular Node; Humans; Structure-Activity Relationship
PubMed: 15368340
DOI: 10.1002/ar.a.20108 -
Journal of the American Heart... Dec 2021Background Left atrial (LA) and right ventricular (RV) performance play an integral role in the pathophysiology and prognosis of heart failure. We hypothesized that...
Background Left atrial (LA) and right ventricular (RV) performance play an integral role in the pathophysiology and prognosis of heart failure. We hypothesized that subclinical left ventricular dysfunction adversely affects LA/RV geometry and function even in a preclinical setting. This study aimed to investigate the atrioventricular and ventricular functional interdependence in a community-based cohort without overt cardiovascular disease. Methods and Results Left ventricular global longitudinal strain (LVGLS), RV free-wall longitudinal strain and LA phasic strain were assessed by speckle-tracking echocardiography in 1080 participants (600 men; 62±12 years) between 2014 and 2018. One hundred and forty-three participants (13.2%) had an abnormal LVGLS (>-18.6%). LA reservoir strain, conduit strain, and RV free-wall longitudinal strain were significantly decreased in abnormal LVGLS group compared with normal LVGLS group (all <0.001). LA and RV dysfunction (LA reservoir strain<31.4% and RVLS>-19.2%) were present in 18.9% and 19.6% of participants with abnormal LVGLS. Decreased LVGLS was associated with worse LA reservoir strain, conduit strain and RV free-wall longitudinal strain (standardized β=-0.20, -0.19 and 0.11 respectively, all <0.01) independent of cardiovascular risk factors. LA and/or RV dysfunction concomitant with abnormal LVGLS carried significantly increased risk of elevated B-type natriuretic peptide levels (>28.6 pg/mL for men and >44.4 pg/mL for women) compared with normal LVGLS (odds ratio, 2.01; =0.030). Conclusions LA/RV dysfunction was present in 20% individuals with abnormal LVGLS and multi-chamber impairment was associated with elevated B-type natriuretic peptide level, which may provide valuable insights for a better understanding of atrioventricular and ventricular interdependence and possibly heart failure preventive strategies.
Topics: Aged; Atrioventricular Node; Heart Diseases; Humans; Middle Aged; Ventricular Function
PubMed: 34775816
DOI: 10.1161/JAHA.121.021624 -
Anatomical Record (Hoboken, N.J. : 2007) Jan 2019The RHOA-ROCK signaling pathway is involved in numerous developmental processes, including cell proliferation, differentiation and migration. RHOA is expressed in the...
The RHOA-ROCK signaling pathway is involved in numerous developmental processes, including cell proliferation, differentiation and migration. RHOA is expressed in the atrioventricular node (AVN) and altered expression of RHOA results in atrioventricular (AV) conduction disorders in mice. The current study aims to detect functional AVN disorders after disturbing RHOA-ROCK signaling in chicken embryos. RHOA-ROCK signaling was inhibited chemically by using the Rho-kinase inhibitor compound Y-27632 in avian embryos (20 experimental and 29 control embryos). Morphological examination of control embryos show a myocardial sinus venosus to atrioventricular canal continuity, contributing to the transitional zone of the AVN. ROCK inhibited embryos revealed lateralization and diminished myocardial sinus venosus to atrioventricular canal continuity and at the severe end of the phenotype hypoplasia of the AVN region. Ex ovo micro-electrode recordings showed an AV conduction delay in all treated embryos as well as cases with first, second (Wenkebach and Mobitz type) and third-degree AV block which could be explained by the spectrum of severity of the morphological phenotype. Laser capture microdissection and subsequent qPCR of tissue collected from this region revealed disturbed expression of HCN1, ISL1, and SHOX2. We conclude that RHOA-ROCK signaling is essential for normal morphological development of the myocardial continuity between the sinus venosus and AVN, contributing to the transitional zone, and possibly the compact AVN region. Disturbing the RHOA-ROCK signaling pathway results in AV conduction disturbances including AV block. The RHOA-ROCK inhibition model can be used to further study the pathophysiology and therapeutic strategies for AV block. Anat Rec, 302:83-92, 2019. © 2018 Wiley Periodicals, Inc.
Topics: Animals; Atrioventricular Block; Atrioventricular Node; Cell Differentiation; Chick Embryo; Chickens; Protein Kinase Inhibitors; Signal Transduction; rho-Associated Kinases; rhoA GTP-Binding Protein
PubMed: 30412368
DOI: 10.1002/ar.23912 -
Scientific Reports Feb 2019The atrioventricular node (AVN) coordinates the timing of atrial and ventricular contraction to optimize cardiac performance. To study this critical function using mouse...
The atrioventricular node (AVN) coordinates the timing of atrial and ventricular contraction to optimize cardiac performance. To study this critical function using mouse genetics, however, new reagents are needed that allow AVN-specific manipulation. Here we describe a novel Gjd3-CreEGFP mouse line that successfully recombines floxed alleles within the AVN beginning at E12.5. These mice have been engineered to express CreEGFP under the control of endogenous Gjd3 regulatory elements without perturbing native protein expression. Detailed histological analysis of Gjd3-CreEGFP mice reveals specific labeling of AVN cardiomyocytes and a subset of cardiac endothelial cells. Importantly, we show that Gjd3-CreEGFP mice have preserved cardiac mechanical and electrical function. In one application of our newly described mouse line, we provide a three-dimensional (3D) view of the AVN using tissue clearing combined with confocal microscopy. With this 3D model as a reference, we identify specific AVN sub-structures based on marker staining characteristics. In addition, we use our Gjd3-CreEGFP mice to guide microdissection of the AVN and construction of a single-cell atlas. Thus, our results establish a new transgenic tool for AVN-specific recombination, provide an updated model of AVN morphology, and describe a roadmap for exploring AVN cellular heterogeneity.
Topics: Action Potentials; Animals; Atrioventricular Node; Connexins; Endothelial Cells; ErbB Receptors; Gene Knock-In Techniques; Heart Atria; Integrases; Mice; Myocytes, Cardiac
PubMed: 30765799
DOI: 10.1038/s41598-019-38683-8 -
PloS One 2020Localization of the components of the cardiac conduction system (CCS) is essential for many therapeutic procedures in cardiac surgery and interventional cardiology....
Localization of the components of the cardiac conduction system (CCS) is essential for many therapeutic procedures in cardiac surgery and interventional cardiology. While histological studies provided fundamental insights into CCS localization, this information is incomplete and difficult to translate to aid in intraprocedural localization. To advance our understanding of CCS localization, we set out to establish a framework for quantifying nodal region morphology. Using this framework, we quantitatively analyzed the sinoatrial node (SAN) and atrioventricular node (AVN) in ovine with postmenstrual age ranging from 4.4 to 58.3 months. In particular, we studied the SAN and AVN in relation to the epicardial and endocardial surfaces, respectively. Using anatomical landmarks, we excised the nodes and adjacent tissues, sectioned those at a thickness of 4 μm at 100 μm intervals, and applied Masson's trichrome stain to the sections. These sections were then imaged, segmented to identify nodal tissue, and analyzed to quantify nodal depth and superficial tissue composition. The minimal SAN depth ranged between 20 and 926 μm. AVN minimal depth ranged between 59 and 1192 μm in the AVN extension region, 49 and 980 μm for the compact node, and 148 and 888 μm for the transition to His Bundle region. Using a logarithmic regression model, we found that minimal depth increased logarithmically with age for the AVN (R2 = 0.818, P = 0.002). Also, the myocardial overlay of the AVN was heterogeneous within different regions and decreased with increasing age. Age associated alterations of SAN minimal depth were insignificant. Our study presents examples of characteristic tissue patterns superficial to the AVN and within the SAN. We suggest that the presented framework provides quantitative information for CCS localization. Our studies indicate that procedural methods and localization approaches in regions near the AVN should account for the age of patients in cardiac surgery and interventional cardiology.
Topics: Animals; Atrioventricular Node; Sheep; Sinoatrial Node
PubMed: 32379798
DOI: 10.1371/journal.pone.0232618 -
American Journal of Physiology. Heart... Jan 2014The atrioventricular (AV) node conducts slowly and has a long refractory period. These features sustain the filtering of atrial impulses and hence are often modulated to... (Review)
Review
The atrioventricular (AV) node conducts slowly and has a long refractory period. These features sustain the filtering of atrial impulses and hence are often modulated to optimize ventricular rate during supraventricular tachyarrhythmias. The AV node is also the site of a clinically common reentrant arrhythmia. Its function is assessed for a variety of purposes from its responses to a premature protocol (S1S2, test beats introduced at different cycle lengths) repeatedly performed at different basic rates and/or to an incremental pacing protocol (increasingly faster rates). Puzzlingly, resulting data and interpretation differ with protocols as well as with chosen recovery and refractory indexes, and are further complicated by the presence of built-in fast and slow pathways. This problem applies to endocavitary investigations of arrhythmias as well as to many experimental functional studies. This review supports an integrated framework of rate-dependent and dual pathway AV nodal function that can account for these puzzling characteristics. The framework was established from AV nodal responses to S1S2S3 protocols that, compared with standard S1S2 protocols, allow for an orderly quantitative dissociation of the different factors involved in changes in AV nodal conduction and refractory indexes under rate-dependent and dual pathway function. Although largely based on data from experimental studies, the proposed framework may well apply to the human AV node. In conclusion, the rate-dependent and dual pathway properties of the AV node can be integrated within a common functional framework the contribution of which to individual responses can be quantitatively determined with properly designed protocols and analytic tools.
Topics: Action Potentials; Animals; Atrioventricular Node; Humans; Muscle Fatigue; Myocardial Contraction; Refractory Period, Electrophysiological
PubMed: 24213614
DOI: 10.1152/ajpheart.00516.2013 -
JACC. Clinical Electrophysiology Mar 2017Pediatric electrophysiologists specialize in the diagnosis and treatment of rhythm abnormalities in pediatric, congenital heart disease, and inherited arrhythmia... (Review)
Review
Pediatric electrophysiologists specialize in the diagnosis and treatment of rhythm abnormalities in pediatric, congenital heart disease, and inherited arrhythmia syndrome patients. The field originated out of the unique knowledge base that rhythm management in young patients required. In the 1970s, pediatric electrophysiology was recognized as a distinct cardiac subspecialty and it has evolved rapidly since that time. Despite the considerable growth in personnel, technology, and complexity that the field has undergone, further opportunities to progress pediatric electrophysiology exist. In this review, we highlight some of the clinical focus of pediatric and adult congenital electrophysiologists to date and identify areas within this specialty where the pediatric and congenital electrophysiology community could come together in order to drive improvements in rhythm management for patients.
Topics: Adult; Arrhythmias, Cardiac; Atrioventricular Node; Cardiac Electrophysiology; Cardiac Resynchronization Therapy; Catheter Ablation; Child; Defibrillators, Implantable; Heart Defects, Congenital; Humans; Postoperative Complications
PubMed: 29759513
DOI: 10.1016/j.jacep.2017.01.008