Journal of APPLIED BIOMEDICINE
ISSN 1214-0287 (on-line)
ISSN 1214-021X (printed)

Volume 5 (2007), No 3, p 115-123




Development of cardiac conduction system in mammals with a focus on the anatomical, functional and medical/genetical aspects

David Sedmera

Address: David Sedmera, Institute of Animal Physiology and Genetics, Videnska 1083, 142 20 Prague 4 - Krc, Czech Republic
sedmera@iapg.cas.cz

Received 5th April 2007.
Revised 17th July 2007.
Published online 15th August 2007.

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SUMMARY
Recent progress in search of mechanisms regulating the spatio-temporal formation of specialized conduction tissues pushes us further in our understanding of the developmental molecular mechanisms of myocardial patterning. It is not clear which mechanisms direct the fates of chamber myocytes to differentiate into ventricular cardiac conduction system (CCS). Similarly, the formation and nature of connections between its most distal component, the Purkinje fibers, and the working myocytes, is unresolved. The process of remodelling of originally ring-like AV junction into AV node and accompanying fibrous insulation between the atria and ventricles is poorly understood, especially on the molecular level. Perturbation of this process can result in abnormal atrio-ventricular connections, manifesting as Wolf-Parkinson-White syndrome of ventricular pre-excitation. Understanding the signalling mechanisms involved in CCS development may be of significance to clinicians and basic researchers studying adult cardiac disease. Congenital abnormalities in CCS, as well as ectopic or inappropriate induction of CCS tissue in the mature heart, may be processes that contribute to, or cause, cardiac conduction disturbance and arrhythmia in adults. Understanding the signalling mechanisms that give rise to normal development of the CCS may thus provide insight into cardiac disease.

KEY WORDS
myocyte; AV junction; Wolf-Parkinson-White syndrome; ventricular CCS; cardiac disease


REFERENCES
Alanis J, Benitez D, Lopez E, Martinez-Palomo A: Impulse propagation through the cardiac junctional regions of the axolotl and the turtle. Jpn J Physiol 23:149-164, 1973.

Anderson RH, Ho SY: The architecture of the sinus node, the atrioventricular conduction axis, and the internodal atrial myocardium. J Cardiovasc Electrophysiol 9:1233-1248, 1998.

Arbel ER, Liberthson R, Langendorf R, Pick A, Lev M, Fishman AP: Electrophysiological and anatomical observations on the heart of the African lungfish. Am J Physiol 232:H24-H34, 1977.

Arguello C, Alanis J, Pantoja O, Valenzuela B: Electrophysiological and ultrastructural study of the atrioventricular canal during the development of the chick embryo. J Mol Cell Cardiol 18:499-510, 1986.

Benson DW, Silberbach GM, Kavanaugh-McHugh A, Cottrill C, Zhang Y, Riggs S, Smalls O, Johnson MC, Watson MS, Seidman JG, Seidman CE, Plowden J, Kugler JD: Mutations in the cardiac transcription factor Nkx2.5 affect diverse cardiac developmental pathways. J Clin Invest 104:1567-1573, 1999.

Benson DW: Genetics of atrioventricular conduction disease in humans. Anat Rec A Discov Mol Cell Evol Biol 280:934-939, 2004.

Cheng G, Litchenberg WH, Cole GJ, Mikawa T, Thompson RP, Gourdie RG: Development of the cardiac conduction system involves recruitment within a multipotent cardiomyogenic lineage. Development 126:5041-5049, 1999.

Christian E, Grigg GC: Electrical activation of the ventricular myocardium of the crocodile Crocodylus johnstoni: a combined microscopic and electrophysiological study. Comp Biochem Physio, Part A Mol Integr Physiol 123:17-23, 1999.

Christoffels VM, Burch JB, Moorman AF: Architectural plan for the heart: Early patterning and delineation of the chambers and the nodes. Trends Cardiovasc Med 14:301-307, 2004.

Chuck ET, Freeman DM, Watanabe M, Rosenbaum DS: Changing activation sequence in the embryonic chick heart. Implications for the development of the His-Purkinje system. Circ Res 81:470-476, 1997.

Coppen SR, Severs NJ, Gourdie RG: Connexin45 (alpha 6) expression delineates an extended conduction system in the embryonic and mature rodent heart. Dev Genet 24:82-90, 1999.

Coppen SR, Kaba RA, Halliday D, Dupont E, Skepper JN, Elneil S, Severs NJ: Comparison of connexin expression patterns in the developing mouse heart and human foetal heart. Mol Cell Biochem 242:121-127, 2003.

Davis DL, Edwards AV, Juraszek AL, Phelps A, Wessels A, Burch JB: A GATA-6 gene heartregion- specific enhancer provides a novel means to mark and probe a discrete component of the mouse cardiac conduction system. Mech Dev 108:105-119, 2001.

de Jong F, Opthof T, Wilde AA, Janse MJ, Charles R, Lamers WH, Moorman AF: Persisting zones of slow impulse conduction in developing chicken hearts. Circ Res 71:240-250, 1992.

Delorme B, Dahl E, Jarry-Guichard T, Marics I, Briand JP, Willecke K, Gros D, Theveniau- Ruissy M: Developmental regulation of connexin 40 gene expression in mouse heart correlates with the differentiation of the conduction system. Dev Dyn 204:358-371, 1995.

Dillon S, Morad M: A new laser scanning system for measuring action potential propagation in the heart. Science 214:453-456, 1981.

Dobrzynski H, Boyett MR, Anderson RH: New insights into pacemaker activity: promoting understanding of sick sinus syndrome. Circulation 115:1921-1932, 2007.

Efimov IR, Aguel F, Cheng Y, Wollenzier B, Trayanova N: Virtual electrode polarization in the far field: implications for external defibrillation. Am J Physiol Heart Circ Physiol 279:H1055-H1070, 2007.

Franco D, Icardo JM: Molecular characterization of the ventricular conduction system in the developing mouse heart: topographical correlation in normal and congenitally malformed hearts. Cardiovasc Res 49:417-429, 2001.

Gassanov N, Er F, Zagidullin N, Hoppe UC: Endothelin induces differentiation of ANPEGFP expressing embryonic stem cells towards a pacemaker phenotype. FASEB J 18:1710-1712, 2004.

Gorza L, Schiaffino S, Vitadello M: Heart conduction system: a neural crest derivative? Brain Res 457:360-366, 1988.

Gorza L, Vettore S, Vitadello M: Molecular and cellular diversity of heart conduction system myocytes. Trends Cardiovasc Med 4:153-159, 1994.

Gourdie RG, Mima T, Thompson RP, Mikawa T: Terminal diversification of the myocyte lineage generates Purkinje fibers of the cardiac conduction system. Development 121:1423-1431, 1995.

Gourdie RG, Wei Y, Kim D, Klatt SC, Mikawa T: Endothelin-induced conversion of embryonic heart muscle cells into impulse-conducting Purkinje fibers. Proc Natl Acad Sci U.S.A. 95:6815-6818, 1998.

Gourdie RG, Harris BS, Bond J, Justus C, Hewett KW, O'Brien TX, Thompson RP, Sedmera D: Development of the cardiac pacemaking and conduction system. Birth Defects Res 69C:46-57, 2003.

Gurjarpadhye A, Hewett KW, Justus C, Wen X, Stadt H, Kirby ML, Sedmera D, Gourdie RG: Cardiac neural crest ablation inhibits compaction and electrical function of conduction system bundles. Am J Physiol Heart Circ Physiol 292:H1291-H1300, 2007.

Harris BS, Spruill L, Edmonson AM, Rackley MS, Benson DW, O'Brien TX, Gourdie RG: Differentiation of cardiac Purkinje fibers requires precise spatiotemporal regulation of Nkx2.5 expression. Dev Dyn 235:38-49, 2006.

Hoogaars WM, Engel A, Brons JF, Verkerk AO, de Lange FJ, Wong LY, Bakker ML, Clout DE, Wakker V, Barnett P, Ravesloot JH, Moorman AF, Verheijck EE, Christoffels VM: Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria. Genes Dev 21:1098-1112, 2007.

Irisawa H: Comparative physiology of the cardiac pacemaker mechanism. Physiol Rev 58:461-498, 1978.

Jay PY, Berul CI, Tanaka M, Ishii M, Kurachi Y, Izumo S: Cardiac conduction and arrhythmia: insights from Nkx2.5 mutations in mouse and humans. In Chadwick DJ, Goode J (eds.): Development of the Cardiac Conduction System. Wiley, Chicheter 2003, pp. 227-241.

Jay PY, Harris BS, Maguire CT, Buerger A, Wakimoto H, Tanaka M, Kupershmidt S, Roden DM, Schultheiss TM, O'Brien TX, Gourdie RG, Berul CI, Izumo S: Nkx2.5 mutation causes anatomic hypoplasia of the cardiac conduction system. J Clin Invest 113:1130-1137, 2004.

Kamino K: Optical approaches to ontogeny of electrical activity and related functional organization during early heart development. Physiol Rev 71:53-91, 1991.

Kokubo H, Tomita-Miyagawa S, Hamada Y, Saga Y: Hesr1 and Hesr2 regulate atrioventricular boundary formation in the developing heart through the repression of Tbx2. Development 134:747-755, 2007.

Kolditz DP, Wijffels MC, Blom NA, van der Laarse A, Markwald RR, Schalij MJ, Gittenberger-de Groot AC: Persistence of functional atrioventricular accessory pathways in postseptated embryonic avian hearts: implications for morphogenesis and functional maturation of the cardiac conduction system. Circulation 115:17-26, 2007.

Litchenberg WH, Norman LW, Holwell AK, Martin KL, Hewett KW, Gourdie RG: The rate and anisotropy of impulse propagation in the postnatal terminal crest are correlated with remodeling of Cx43 gap junction pattern. Cardiovasc Res 45:379-387, 2000.

Liu J, Dobrzynski H, Yanni J, Boyett MR, Lei M: Organisation of the mouse sinoatrial node: structure and expression of HCN channels. Cardiovasc Res 73:729-738, 2007.

Lyons GE, Schiaffino S, Sassoon D, Barton P, Buckingham M: Developmental regulation of myosin gene expression in mouse cardiac muscle. J Cell Biol 111:2427-2436, 1990.

Lyons I, Parsons LM, Hartley L, Li R, Andrews JE, Robb L, Harvey RP: Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2.5. Genes Dev 9:1654-1666, 1995.

Meilhac SM, Kelly RG, Rocancourt D, Eloy- Trinquet S, Nicolas JF, Buckingham ME: A retrospective clonal analysis of the myocardium reveals two phases of clonal growth in the developing mouse heart. Development 130:3877-3889, 2003.

Meysen S, Marger L, Hewett KW, Jarry-Guichard T, Agarkova I, Chauvin JP, Perriard JC, Izumo S, Gourdie RG, Mangoni ME, Nargeot J, Gros D, Miquerol L: Nkx2.5 cellautonomous gene function is required for the postnatal formation of the peripheral ventricular conduction system. Dev Biol 303:740-753, 2007.

Miquerol L, Meysen S, Mangoni M, Bois P, van Rijen HV, Abran P, Jongsma H, Nargeot J, Gros D: Architectural and functional asymmetry of the His-Purkinje system of the murine heart. Cardiovasc Res 63:77-86, 2004.

Mommersteeg MT, Hoogaars WM, Prall OW, de Gier-de Vries C, Wiese C, Clout DE, Papaioannou VE, Brown NA, Harvey RP, Moorman AF, Christoffels VM: Molecular pathway for the localized formation of the sinoatrial node. Circ Res 100:354-362, 2007.

Moorman AF, de Jong F, Denyn MM, Lamers WH: Development of the cardiac conduction system. Circ. Res. 82:629-644, 1998. Moorman AF, Christoffels VM: Cardiac chamber formation: development, genes, and evolution. Physiol Rev 83:1223-1267, 2003.

Moskowitz IP, Pizard A, Patel VV, Bruneau BG, Kim JB, Kupershmidt S, Roden D, Berul CI, Seidman CE, Seidman JG: The T-Box transcription factor Tbx5 is required for the patterning and maturation of the murine cardiac conduction system. Development 131:4107-4116, 2004.

Myers DC, Fishman GI: Toward an understanding of the genetics of murine cardiac pacemaking and conduction system development. Anat Rec 280A:1018-1021, 2004.

Nakamura T, Colbert MC, Robbins J: Neural crest cells retain multipotential characteristics in the developing valves and label the cardiac conduction system. Circ Res 98:1547-1554, 2006.

Nygren A, Clark RB, Belke DD, Kondo C, Giles WR, Witkowski FX: Voltage-sensitive dye mapping of activation and conduction in adult mouse hearts. Ann Biomed Eng 28:958-967, 2000.

Ozcelik C, Erdmann B, Pilz B, Wettschureck N, Britsch S, Hubner N, Chien KR, Birchmeier C, Garratt AN: Conditional mutation of the ErbB2 (HER2) receptor in cardiomyocytes leads to dilated cardiomyopathy. Proc Natl Acad Sci U.S.A. 99:8880-8885, 2002.

Pashmforoush M, Lu JT, Chen H, Amand TS, Kondo R, Pradervand S, Evans SM, Clark B, Feramisco JR, Giles W, Ho SY, Benson DW, Silberbach M, Shou W, Chien KR: Nkx2.5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block. Cell 117:373-386, 2004.

Patel R, Kos L: Endothelin-1 and Neuregulin-1 convert embryonic cardiomyocytes into cells of the conduction system in the mouse. Dev Dyn 233:20-28, 2005.

Pennisi DJ, Rentschler S, Gourdie RG, Fishman GI, Mikawa T: Induction and patterning of the cardiac conduction system. Int J Dev Biol 46:765-775 2002.

Reckova M, Rosengarten C, deAlmeida A, Stanley CP, Wessels A, Gourdie RG, Thompson RP, Sedmera D: Hemodynamics is a key epigenetic factor in development of the cardiac conduction system. Circ Res 93:77-85, 2003.

Rentschler S, Vaidya DM, Tamaddon H, Degenhardt K, Sassoon D, Morley GE, Jalife J, Fishman GI: Visualization and functional characterization of the developing murine cardiac conduction system. Development 128:1785-1792, 2001.

Rentschler S, Zander J, Meyers K, France D, Levine R, Porter G, Rivkees SA, Morley GE, Fishman GI: Neuregulin-1 promotes formation of the murine cardiac conduction system. Proc Natl Acad Sci U.S.A. 99:10464-10469, 2002.

Robb JS: Comparative Basic Cardiology. Grune & Stratton, New York and London 1965.

Rosen MR, Robinson RB, Brink P, Cohen IS: Recreating the biological pacemaker. Anat Rec A Discov Mol Cell Evol Biol 280:1046-1052, 2004.

Rothenberg F, Nikolski V, Watanabe M, Efimov I: Electrophysiology and anatomy of embryonic rabbit hearts before and after septation. Am J Physiol Heart Circ Physiol 288:H344-H351, 2005.

Sanders E, de Groot IJ, Geerts WJ, de Jong F, van Horssen AA, Los JA, Moorman AF: The local expression of adult chicken heart myosins during development. II. Ventricular conducting tissue. Anat Embryol 174:187-193, 1986.

Sedmera D, Reckova M, DeAlmeida A, Sedmerova M, Biermann M, Volejnik J, Sarre A, Raddatz E, McCarthy RA, Gourdie RG, Thompson RP: Functional and morphological evidence for a ventricular conduction system in the zebrafish and Xenopus heart. Am J Physiol Heart Circ Physiol 284:H1152-H1160, 2003a.

Sedmera D, Reckova M, DeAlmeida A, Coppen SR, Kubalak SW, Gourdie RG, Thompson RP: Spatiotemporal pattern of commitment to slowed proliferation in the embryonic mouse heart indicates progressive differentiation of the cardiac conduction system. Anat Rec 274A:773-777, 2003b.

Sedmera D, Reckova M, Rosengarten C, Torres MI, Gourdie RG, Thompson RP: Optical mapping of electrical activation in developing heart. Microsc Microanal 11:209-215, 2005.

Takebayashi-Suzuki K, Yanagisawa M, Gourdie RG, Kanzawa N, Mikawa T: In vivo induction of cardiac Purkinje fiber differentiation by coexpression of preproendothelin-1 and endothelin converting enzyme-1. Development 127:3523-3532, 2000.

Tamaddon HS, Vaidya D, Simon AM, Paul DL, Jalife J, Morley GE: High-resolution optical mapping of the right bundle branch in connexin40 knockout mice reveals slow conduction in the specialized conduction system. Circ Res 87:929-936, 2000.

Thompson RP, Lindroth JR, Allen AJ, Fazel AR: Cell differentiation birthdates in the embryonic rat heart. Ann N.Y. Acad Sci 588:446-448, 1990.

van Veen TA, van Rijen HV, van Kempen MJ, Miquerol L, Opthof T, Gros D, Vos MA, Jongsma HJ, de Bakker JM: Discontinuous conduction in mouse bundle branches is caused by bundle-branch architecture. Circulation 112:2235-2244, 2005.

Viswanathan S, Burch JB, Fishman GI, Moskowitz IP, Benson DW: Characterization of sinoatrial node in four conduction system marker mice. J Mol Cell Cardiol 42:946-953, 2007.

Wessels A, Markman MW, Vermeulen JL, Anderson RH, Moorman AF, Lamers WH: The development of the atrioventricular junction in the human heart. Circ Res 78:110-117, 1996.

Wolf CM, Berul CI: Inherited conduction system abnormalities-one group of diseases, many genes. J Cardiovasc Electrophysiol 17:446-455, 2006.
CITED

Sedmera D, McQuinn T: Embryogenesis of the Heart Muscle. Heart Failure Clinics 4:235-245, 2008.


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