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7. Structure, function and clinical relevance of the cardiac conduction system, including the atrioventricular ring and outflow tract tissues

Author

Dobrzynski, Halina, Anderson, Robert H., Atkinson, Andrew, Borbas, Zoltan, DʼSouza, Alicia, Fraser, John F., Inada, Shin, Logantha, Sunil J.R.J., Monfredi, Oliver, Morris, Gwilym M., Moorman, Anton F.M., Nikolaidou, Thodora, Schneider, Heiko, Szuts, Viktoria, Temple, Ian P., Yanni, Joseph, and Boyett, Mark R.

Published
2013
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15. Three-dimensional computer model of the right atrium including the sinoatrial and atrioventricular nodes predicts classical nodal behaviours

Author

Li, Jue, Inada, Shin, Schneider, Jurgen E, Zhang, Henggui, Dobrzynski, Halina, and Boyett, Mark R

Subjects
Models, Anatomic, Biophysical Simulations, Computer and Information Sciences, Physiology, Science, Biophysics, Action Potentials, Electrophysiological Properties, Imaging, Three-Dimensional, Heart Conduction System, Atrial Fibrillation, Medicine and Health Sciences, Animals, Computer Simulation, Heart Atria, Computerized Simulations, Sinoatrial Node, Biology and Life Sciences, Heart, Magnetic Resonance Imaging, Electrophysiology, Cardiovascular Anatomy, Atrioventricular Node, cardiovascular system, Medicine, Rabbits, Anatomy, Research Article, Computer Modeling
Abstract

The aim of the study was to develop a three-dimensional (3D) anatomically-detailed model of the rabbit right atrium containing the sinoatrial and atrioventricular nodes to study the electrophysiology of the nodes. A model was generated based on 3D images of a rabbit heart (atria and part of ventricles), obtained using high-resolution magnetic resonance imaging. Segmentation was carried out semi-manually. A 3D right atrium array model (∼3.16 million elements), including eighteen objects, was constructed. For description of cellular electrophysiology, the Rogers-modified FitzHugh-Nagumo model was further modified to allow control of the major characteristics of the action potential with relatively low computational resource requirements. Model parameters were chosen to simulate the action potentials in the sinoatrial node, atrial muscle, inferior nodal extension and penetrating bundle. The block zone was simulated as passive tissue. The sinoatrial node, crista terminalis, main branch and roof bundle were considered as anisotropic. We have simulated normal and abnormal electrophysiology of the two nodes. In accordance with experimental findings: (i) during sinus rhythm, conduction occurs down the interatrial septum and into the atrioventricular node via the fast pathway (conduction down the crista terminalis and into the atrioventricular node via the slow pathway is slower); (ii) during atrial fibrillation, the sinoatrial node is protected from overdrive by its long refractory period; and (iii) during atrial fibrillation, the atrioventricular node reduces the frequency of action potentials reaching the ventricles. The model is able to simulate ventricular echo beats. In summary, a 3D anatomical model of the right atrium containing the cardiac conduction system is able to simulate a wide range of classical nodal behaviours.

Published
2014

16. Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy

Author

Freyermuth, Fernande, primary, Rau, Frédérique, additional, Kokunai, Yosuke, additional, Linke, Thomas, additional, Sellier, Chantal, additional, Nakamori, Masayuki, additional, Kino, Yoshihiro, additional, Arandel, Ludovic, additional, Jollet, Arnaud, additional, Thibault, Christelle, additional, Philipps, Muriel, additional, Vicaire, Serge, additional, Jost, Bernard, additional, Udd, Bjarne, additional, Day, John W., additional, Duboc, Denis, additional, Wahbi, Karim, additional, Matsumura, Tsuyoshi, additional, Fujimura, Harutoshi, additional, Mochizuki, Hideki, additional, Deryckere, François, additional, Kimura, Takashi, additional, Nukina, Nobuyuki, additional, Ishiura, Shoichi, additional, Lacroix, Vincent, additional, Campan-Fournier, Amandine, additional, Navratil, Vincent, additional, Chautard, Emilie, additional, Auboeuf, Didier, additional, Horie, Minoru, additional, Imoto, Keiji, additional, Lee, Kuang-Yung, additional, Swanson, Maurice S., additional, de Munain, Adolfo Lopez, additional, Inada, Shin, additional, Itoh, Hideki, additional, Nakazawa, Kazuo, additional, Ashihara, Takashi, additional, Wang, Eric, additional, Zimmer, Thomas, additional, Furling, Denis, additional, Takahashi, Masanori P., additional, and Charlet-Berguerand, Nicolas, additional

Published
2016
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17. Pharmacological Blockade of I-Ks Destabilizes Spiral-Wave Reentry Under beta-Adrenergic Stimulation in Favor of Its Early Termination

Author

Kato, Sara, Honjo, Haruo, Takemoto, Yoshio, Takanari, Hiroki, Suzuki, Tomoyuki, Okuno, Yusuke, Opthof, Tobias, Sakuma, Ichiro, Inada, Shin, Nakazawa, Kazuo, Ashihara, Takashi, Kodama, Itsuo, Kamiya, Kaichiro, and Cardiology

Subjects
cardiovascular system
Abstract

We tested a hypothesis that an enhancement of I-Ks may play a pivotal role in ventricular proarrhythmia under high sympathetic activity. A 2-dimensional ventricular muscle layer was prepared in rabbit hearts, and action potential signals were analyzed by optical mapping. During constant stimulation, isoproterenol (ISP, 0.1 mu M) significantly shortened action potential duration (APD); chromanol 293B (30 mu M), a selective I-Ks-blocker, reversed the APD shortening. VTs induced in the presence of ISP lasted longer than in the control, and this was reversed by 293B. E-4031 (0.1 mu M), a selective I-Kr-blocker, did not cause such reversal. Spiral-wave (SW) reentry with ISP was characterized by more stable rotation around a shorter functional block line (FBL) than in the control. After application of 293B, SW reentry was destabilized, and rotation around a longer FBL with prominent drift reappeared. The APD abbreviation by ISP close to the rotation center was more pronounced than in the periphery, leading to an opposite APD gradient (center

Published
2012

18. Role of Ca^<2+> Release from Sarcoplasmic Reticulum in Pacemaker Activity of the Sinoatrial Node

Author

HONJO, Haruo, INADA, Shin, NIWA, Ryoko, SHIBATA, Nitaro, MITSUI, Kazuyuki, BOYETT, Mark R., KAMIYA, Kaichiro, and KODAMA, Itsuo

Subjects
sinoatrial node, pacemaker activity, extracellular potential mapping, ryanodine, sarcoplasmic reticulum
Abstract

Recent studies using confocal microscopy combined with patch clamping on single sinoatrial (SA) node pacemaker cells suggest that Ca^ release from the sarcoplasmic reticulum (SR) during diastole may play a prominent role in the late phase of pacemaker depolarization. The present study was designed to test this hypothesis in the intact SA node. We investigated the effects of a high concentration of ryanodine, which is known to disable SR Ca^ release, on spontaneous activity of isolated rabbit right atrium including the whole SA node by using an extracellular potential mapping technique. Inhibition of SR Ca^ release by 30 μM ryanodine caused only a moderate reduction of the spontaneous firing rate (by 20.0±2.8 %, n=4) of the intact SA node. This observation is inconsistent with previous data obtained from single pacemaker cells. Physiological significance of SR Ca^ release in the regulation of SA node pacemaker activity is still unsettled., 国立情報学研究所で電子化したコンテンツを使用している。

Published
2002

20. Biophysical Characterization of the Underappreciated and Important Relationship Between Heart Rate Variability and Heart Rate

Author

Monfredi, Oliver, primary, Lyashkov, Alexey E., additional, Johnsen, Anne-Berit, additional, Inada, Shin, additional, Schneider, Heiko, additional, Wang, Ruoxi, additional, Nirmalan, Mahesh, additional, Wisloff, Ulrik, additional, Maltsev, Victor A., additional, Lakatta, Edward G., additional, Zhang, Henggui, additional, and Boyett, Mark R., additional

Published
2014
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23. Molecular basis of the electrical activity of the atrioventricular junction and Purkinje fibres

Author

Ravens, U, Tripathi, O N, Sanguinetti, M C, Dobrzynski, Halina, Monfredi, Oliver, Greener, Ian, Atkinson, Andrew, Inada, Shin, Taube, Mary-Anne, Yanni, Joseph, Fedorenko, Olga, Molenaar, Peter, Anderson, Robert, Efimov, Igor, Boyett, Mark, Ravens, U, Tripathi, O N, Sanguinetti, M C, Dobrzynski, Halina, Monfredi, Oliver, Greener, Ian, Atkinson, Andrew, Inada, Shin, Taube, Mary-Anne, Yanni, Joseph, Fedorenko, Olga, Molenaar, Peter, Anderson, Robert, Efimov, Igor, and Boyett, Mark

Published
2011

24. Molecular architecture of the human specialised atrioventricular conduction axis

Author

Greener, Ian, Monfredi, Oliver, Inada, Shin, Chandler, Natalie, Tellez, James, Atkinson, Andrew, Taube, M.-A., Billeter, Rudolf, Anderson, Robert, Efimov, Igor, Molenaar, Peter, Sigg, Daniel, Sharma, Vinod, Boyett, Mark, Dobrzynski, Halina, Greener, Ian, Monfredi, Oliver, Inada, Shin, Chandler, Natalie, Tellez, James, Atkinson, Andrew, Taube, M.-A., Billeter, Rudolf, Anderson, Robert, Efimov, Igor, Molenaar, Peter, Sigg, Daniel, Sharma, Vinod, Boyett, Mark, and Dobrzynski, Halina

Published
2011

25. Molecular architecture of the human sinus node: insights into the function of the cardiac pacemaker

Author

Chandler, Natalie, Greener, Ian, Tellez, James, Inada, Shin, Musa, Hanny, Molenaar, Peter, DiFrancesco, Dario, Baruscotti, Mirko, Longhi, Renatp, Anderson, Robert, Billeter, Rudolf, Sharma, Vinod, Sigg, Craig, Boyett, Mark, Dobrzynski, Halina, Chandler, Natalie, Greener, Ian, Tellez, James, Inada, Shin, Musa, Hanny, Molenaar, Peter, DiFrancesco, Dario, Baruscotti, Mirko, Longhi, Renatp, Anderson, Robert, Billeter, Rudolf, Sharma, Vinod, Sigg, Craig, Boyett, Mark, and Dobrzynski, Halina

Abstract

BACKGROUND: Although we know much about the molecular makeup of the sinus node (SN) in small mammals, little is known about it in humans. The aims of the present study were to investigate the expression of ion channels in the human SN and to use the data to predict electrical activity. METHODS AND RESULTS: Quantitative polymerase chain reaction, in situ hybridization, and immunofluorescence were used to analyze 6 human tissue samples. Messenger RNA (mRNA) for 120 ion channels (and some related proteins) was measured in the SN, a novel paranodal area, and the right atrium (RA). The results showed, for example, that in the SN compared with the RA, there was a lower expression of Na(v)1.5, K(v)4.3, K(v)1.5, ERG, K(ir)2.1, K(ir)6.2, RyR2, SERCA2a, Cx40, and Cx43 mRNAs but a higher expression of Ca(v)1.3, Ca(v)3.1, HCN1, and HCN4 mRNAs. The expression pattern of many ion channels in the paranodal area was intermediate between that of the SN and RA; however, compared with the SN and RA, the paranodal area showed greater expression of K(v)4.2, K(ir)6.1, TASK1, SK2, and MiRP2. Expression of ion channel proteins was in agreement with expression of the corresponding mRNAs. The levels of mRNA in the SN, as a percentage of those in the RA, were used to estimate conductances of key ionic currents as a percentage of those in a mathematical model of human atrial action potential. The resulting SN model successfully produced pacemaking. CONCLUSIONS: Ion channels show a complex and heterogeneous pattern of expression in the SN, paranodal area, and RA in humans, and the expression pattern is appropriate to explain pacemaking.

Published
2009

30. Pharmacological Blockade of IKs Destabilizes Spiral-Wave Reentry Under &beta;-Adrenergic Stimulation in Favor of Its Early Termination

Author

Kato, Sara, primary, Honjo, Haruo, additional, Takemoto, Yoshio, additional, Takanari, Hiroki, additional, Suzuki, Tomoyuki, additional, Okuno, Yusuke, additional, Opthof, Tobias, additional, Sakuma, Ichiro, additional, Inada, Shin, additional, Nakazawa, Kazuo, additional, Ashihara, Takashi, additional, Kodama, Itsuo, additional, and Kamiya, Kaichiro, additional

Published
2012
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34. Computer Three‐Dimensional Anatomical Reconstruction of the Human Sinus Node and a Novel Paranodal Area

Author

Chandler, Natalie, primary, Aslanidi, Oleg, additional, Buckley, David, additional, Inada, Shin, additional, Birchall, Steven, additional, Atkinson, Andrew, additional, Kirk, Danielle, additional, Monfredi, Oliver, additional, Molenaar, Peter, additional, Anderson, Robert, additional, Sharma, Vinod, additional, Sigg, Daniel, additional, Zhang, Henggui, additional, Boyett, Mark, additional, and Dobrzynski, Halina, additional

Published
2011
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40. Molecular Architecture of the Human Sinus Node

Author

Chandler, Natalie J., primary, Greener, Ian D., additional, Tellez, James O., additional, Inada, Shin, additional, Musa, Hanny, additional, Molenaar, Peter, additional, DiFrancesco, Dario, additional, Baruscotti, Mirko, additional, Longhi, Renato, additional, Anderson, Robert H., additional, Billeter, Rudolf, additional, Sharma, Vinod, additional, Sigg, Daniel C., additional, Boyett, Mark R., additional, and Dobrzynski, Halina, additional

Published
2009
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42. Computer Three-Dimensional Reconstruction of the Atrioventricular Node

Author

Li, Jue, primary, Greener, Ian D., additional, Inada, Shin, additional, Nikolski, Vladimir P., additional, Yamamoto, Mitsuru, additional, Hancox, Jules C., additional, Zhang, Henggui, additional, Billeter, Rudi, additional, Efimov, Igor R., additional, Dobrzynski, Halina, additional, and Boyett, Mark R., additional

Published
2008
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48. Ageing-dependent remodelling of ion channel and Ca2+ clock genes underlying sino-atrial node pacemaking.

Author

Tellez, James O., Mączewski, Michal, Yanni, Joseph, Sutyagin, Pavel, Mackiewicz, Urszula, Atkinson, Andrew, Inada, Shin, Beresewicz, Andrzej, Billeter, Rudi, Dobrzynski, Halina, and Boyett, M. R.

Subjects
AGING, ION channels, CALCIUM channels, CARDIAC pacemakers, GENE expression, ELECTROPHYSIOLOGY, LABORATORY rats
Abstract

The function of the sino-atrial node (SAN), the pacemaker of the heart, is known to decline with age, resulting in pacemaker disease in the elderly. The aim of the study was to investigate the effects of ageing on the SAN by characterizing electrophysiological changes and determining whether changes in gene expression are involved. In young and old rats, SAN function was characterized in the anaesthetized animal, isolated heart and isolated right atrium using ECG and action potential recordings; gene expression was characterized using quantitative PCR. The SAN function declined with age as follows: the intrinsic heart rate declined by 18 ± 3%; the corrected SAN recovery time increased by 43 ± 13%; and the SAN action potential duration increased by 11 ± 3% (at 75% repolarization). Gene expression in the SAN changed considerably with age, e.g. there was an age-dependent decrease in the Ca2+ clock gene, RYR2, and changes in many ion channels (e.g. increases in Nav1.5, Navβ1 and Cav1.2 and decreases in Kv1.5 and HCN1). In conclusion, with age, there are changes in the expression of ion channel and Ca2+ clock genes in the SAN, and the changes may provide a partial explanation for the age-dependent decline in pacemaker function. [ABSTRACT FROM AUTHOR]

Published
2011
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49. Computer Three-Dimensional Reconstruction of the Atrioventricular Node.

Author

Jue Li, Greener, Ian D., Inada, Shin, Nikolski, Vladimir P., Yamamoto, Mitsuru, Hancox, Jules C., Henggui Zhang, Billeter, Rudi, Efimov, Igor R., Dobrzynski, Halina, and Boyett, Mark R.

Subjects
ATRIOVENTRICULAR node, HEART conduction system, HEART, HEART beat, HIS bundle
Abstract

The article presents an anatomic model of the atrioventricular node (AVN) and relate it to AVN function. The anatomic model demonstrates the importance of the inferior nodal extension (INE) pacemaking and atrioventricular nodal reentry. The model can also be used to simulate the activation sequence of the AVN during normal anterograde conduction through the AVN, atrioventricular junctional pacemaking, and slow-fast and fast-slow atrioventricular nodal reentry.

Published
2008
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