Gap junctions in cardiovascular disease.

Connexins, the protein molecules forming gap junction channels, are reduced in number or redistributed from intercalated disks to lateral cell borders in a variety of cardiac diseases. This "gap junction remodeling" is considered to be arrhythmogenic. Using a simple model of human ventricular myocardium, we found that quantitative remodeling data extracted from the literature gave rise to only small to moderate changes in conduction velocity and the anisotropy ratio. Especially for longitudinal conduction, cytoplasmic resistivity (and thus cellular geometry) is much more important than commonly realized. None of the remodeling data gave rise to slow conduction on the order of a few centimeters per second.

[1]  P. Brink,et al.  Formation of heterotypic gap junction channels by connexins 40 and 43. , 2000, Circulation research.

[2]  J. Pepper,et al.  Downregulation of immunodetectable connexin43 and decreased gap junction size in the pathogenesis of chronic hibernation in the human left ventricle. , 1998, Circulation.

[3]  Y. Takagishi,et al.  Remodeling of gap junctional coupling in hypertrophied right ventricles of rats with monocrotaline-induced pulmonary hypertension. , 2000, Circulation research.

[4]  N S Peters,et al.  Disturbed connexin43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia. , 1997, Circulation.

[5]  C. Fry,et al.  An analysis of the cable properties of frog ventricular myocardium. , 1978, The Journal of physiology.

[6]  R Wilders,et al.  Effects of ischemia on discontinuous action potential conduction in hybrid pairs of ventricular cells. , 1999, Circulation.

[7]  C. Green,et al.  Altered patterns of gap junction distribution in ischemic heart disease. An immunohistochemical study of human myocardium using laser scanning confocal microscopy. , 1991, The American journal of pathology.

[8]  D. Zipes,et al.  Radiofrequency catheter ablation of the atria eliminates pacing-induced sustained atrial fibrillation and reduces connexin 43 in dogs. , 1997, Circulation.

[9]  A. Kleber,et al.  Slow conduction in cardiac tissue, I: effects of a reduction of excitability versus a reduction of electrical coupling on microconduction. , 1998, Circulation research.

[10]  P. Brink,et al.  Evidence for heteromeric gap junction channels formed from rat connexin43 and human connexin37. , 1997, American journal of physiology. Cell physiology.

[11]  S. Taffet,et al.  Connexin diversity and gap junction regulation by pHi. , 1999, Developmental genetics.

[12]  N. Gilula,et al.  The Gap Junction Communication Channel , 1996, Cell.

[13]  J E Saffitz,et al.  Distribution and Three‐Dimensional Structure of Intercellular Junctions in Canine Myocardium , 1989, Circulation research.

[14]  C. Green,et al.  Validation of immunohistochemical quantification in confocal scanning laser microscopy: a comparative assessment of gap junction size with confocal and ultrastructural techniques. , 1993, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[15]  J E Saffitz,et al.  Gap Junction Protein Phenotypes of the Human Heart and Conduction System , 1995, Journal of cardiovascular electrophysiology.

[16]  M. Spach,et al.  The stochastic nature of cardiac propagation at a microscopic level. Electrical description of myocardial architecture and its application to conduction. , 1995, Circulation research.

[17]  Y Rudy,et al.  Ionic mechanisms of propagation in cardiac tissue. Roles of the sodium and L-type calcium currents during reduced excitability and decreased gap junction coupling. , 1997, Circulation research.

[18]  M S Spach,et al.  Anisotropy of Cardiac Tissue: , 1999, Journal of cardiovascular electrophysiology.

[19]  J. Haefliger,et al.  Connexin40, a component of gap junctions in vascular endothelium, is restricted in its ability to interact with other connexins. , 1993, Molecular biology of the cell.

[20]  N. Severs,et al.  Connexin45 (alpha 6) expression delineates an extended conduction system in the embryonic and mature rodent heart. , 1999, Developmental genetics.

[21]  N. Severs,et al.  Connexin45 expression is preferentially associated with the ventricular conduction system in mouse and rat heart. , 1998, Circulation research.

[22]  M. Allessie,et al.  Gap junctional remodeling in relation to stabilization of atrial fibrillation in the goat. , 2000, Cardiovascular research.

[23]  R C Barr,et al.  Electrophysiological effects of remodeling cardiac gap junctions and cell size: experimental and model studies of normal cardiac growth. , 2000, Circulation research.

[24]  R. Bruzzone,et al.  The cellular internet: On‐line with connexins , 1996, BioEssays : news and reviews in molecular, cellular and developmental biology.

[25]  K. Willecke,et al.  Cardiac Conduction Abnormalities in Mice Lacking the Gap Junction Protein Connexin40 , 1999, Journal of cardiovascular electrophysiology.

[26]  H. Jongsma,et al.  Jongsma and Wilders Gap Junctions in Cardiovascular Disease , 2000 .

[27]  J. Saffitz,et al.  Rapid turnover of connexin43 in the adult rat heart. , 1998, Circulation research.

[28]  N. Severs,et al.  Altered patterns of cardiac intercellular junction distribution in hypertrophic cardiomyopathy. , 1996, Heart.

[29]  R. Bruzzone,et al.  Connections with connexins: the molecular basis of direct intercellular signaling. , 1996, European journal of biochemistry.

[30]  David L. Paul,et al.  Mice lacking connexin40 have cardiac conduction abnormalities characteristic of atrioventricular block and bundle branch block , 1998, Current Biology.

[31]  D. Beuckelmann,et al.  Simulation study of cellular electric properties in heart failure. , 1998, Circulation research.

[32]  Y Rudy,et al.  Action potential propagation in inhomogeneous cardiac tissue: safety factor considerations and ionic mechanism. , 2000, American journal of physiology. Heart and circulatory physiology.

[33]  A. Moorman,et al.  Differential connexin distribution accommodates cardiac function in different species , 1995, Microscopy research and technique.

[34]  H. Jongsma,et al.  Limitations of the dual voltage clamp method in assaying conductance and kinetics of gap junction channels. , 1992, Biophysical journal.

[35]  E. Page,et al.  Ultrastructural changes during development of gap junctions in rabbit left ventricular myocardial cells. , 1980, Journal of ultrastructure research.

[36]  Y. Shibata,et al.  Freeze-fracture studies of gap junctions in vertebrate cardiac muscle cells , 1979 .

[37]  H. Jongsma,et al.  Connexins in mammalian heart function , 1996, BioEssays : news and reviews in molecular, cellular and developmental biology.

[38]  J. Saffitz,et al.  Multiple connexins colocalize in canine ventricular myocyte gap junctions. , 1993, Circulation research.

[39]  K. Fujimoto,et al.  Remodeling of cell-cell and cell-extracellular matrix interactions at the border zone of rat myocardial infarcts. , 1999, Circulation research.

[40]  R. P. Thompson,et al.  The spatial distribution and relative abundance of gap-junctional connexin40 and connexin43 correlate to functional properties of components of the cardiac atrioventricular conduction system. , 1993, Journal of cell science.

[41]  A. Gerdes,et al.  Chronic pressure overload cardiac hypertrophy and failure in guinea pigs: III. Intercalated disc remodeling. , 1999, Journal of molecular and cellular cardiology.

[42]  M. Bennett,et al.  Clustering of connexin 43-enhanced green fluorescent protein gap junction channels and functional coupling in living cells. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[43]  P. Poole‐Wilson,et al.  Reduced content of connexin43 gap junctions in ventricular myocardium from hypertrophied and ischemic human hearts. , 1993, Circulation.

[44]  A. Matter.  A MORPHOMETRIC STUDY ON THE NEXUS OF RAT CARDIAC MUSCLE , 1973, The Journal of cell biology.

[45]  P. Taggart,et al.  Inhomogeneous transmural conduction during early ischaemia in patients with coronary artery disease. , 2000, Journal of molecular and cellular cardiology.

[46]  M R Boyett,et al.  Connexin45, a Major Connexin of the Rabbit Sinoatrial Node, Is Co-expressed with Connexin43 in a Restricted Zone at the Nodal-Crista Terminalis Border , 1999, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[47]  M. Allessie,et al.  Altered Pattern of Connexin40 Distribution in Persistent Atrial Fibrillation in the Goat , 1998, Journal of cardiovascular electrophysiology.

[48]  A. Moorman,et al.  Restricted distribution of connexin40, a gap junctional protein, in mammalian heart. , 1994, Circulation research.

[49]  B. Lüderitz,et al.  Conduction disturbances and increased atrial vulnerability in Connexin40-deficient mice analyzed by transesophageal stimulation. , 1999, Circulation.

[50]  J E Saffitz,et al.  Remodeling of ventricular conduction pathways in healed canine infarct border zones. , 1991, The Journal of clinical investigation.

[51]  Mary B Wagner,et al.  Electrical interactions among real cardiac cells and cell models in a linear strand. , 1999, American journal of physiology. Heart and circulatory physiology.

[52]  Spach,et al.  Effects of cardiac microstructure on propagating electrical waveforms , 2000, Circulation research.