EDITORIALS
Fine Structure of Internodal Pathways*
BRIAN New
F. HOFFMAN,
MD
York, New York
In this issue of the Journal, Sherf and James1 provide a morphologic description of six different types of cells in the canine and the human atrium. The data are derived from light and electron microscopic studies on tissues obtained from the parts of the atrium-the Eustachian ridge and Bachmann’s bundle-in which earlier studies by James2 located the anterior and posterior internodal tracts. In addition, the authors consider at some length the possible functional significance of each of the different types of cells in relation to normal and abnormal electric activity. Their paper is certain to provide a new impetus for studies on correlations between structure and function in the mammalian atrium and to add new enthusiasm to the argument about specialized internodal pathways that has been waged periodically since 1910. Specialization of Atrial Cells If, as seems likely, the findings by Sherf and James lead to renewed interest in either topic, a serious effort should be made to avoid some of the problems that have confused the issue over the years. First and foremost, it is essential to have clear definitions that are agreed upon by all concerned. Atria1 cells can be called special or specialized if their properties differ significantly from those of the cells that constitute the bulk of the atria1 myocardium. Evidence of specialization might derive from studies on ultrastructure, electrophysiology or other properties. The morphologic evidence of specialization provided by Sherf and James seems to be clear and compelling. Also, as they note, the cells they studied have a location similar to that described for cells or fibers that were specialized in terms of the characteristics of their transmembrane potentials.“*4 It is From the Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York. Manuscript received May 22, 1979. accepted May 29, 1979. Address for reprints: Brian F. Hoffman, MD, Department of Pharmacology, College of Physicians and Surgeons of Columbia University, 630 West 166 Street, New York, New York 10032.
therefore tempting to assume that one or the other of the morphologically specialized cells they describe corresponds to the electrophysiologically specialized atrial plateau fiber. The authors favor the P cell; others might opt for the Purkinje-like celIs. There is very likely a correlation between structural and functional specialization, but additional studies are essential before one can relate, with certainty, functional characteristics to local differences in structure or ultrastructure. If all other properties were the same, fibers with a small cross-sectional area might be expected to conduct less rapidly than larger fibers. However, if the density of channels for the fast inward current were sufficiently lower in the large than in the small fibers, the converse might be true; at present we do not have methods to make the required measurements. Similarly, because it generally is accepted that a path of low electric resistance between cardiac cells is provided by special properties of the gap or tight junction, it is often assumed that some estilpate of the adequacy of intercellular coupling can be made from measurement of the relative density of such junctions. This may not be correct. It seems likely that a path of reasonably low resistance between cells can be provided by a relatively small number of junctional particles in correct apposition. What is required to evaluate the question is the direct determination of the coupling resistance between cells and, for the same cells, appropriate studies on freeze-fractured gap junctions using quantitative techniques. Electric Properties of Atria1 Cells The studies by Sherf and James present a special problem to the electrophysiologist. By means of intracellular microelectrodes it has been possible to record transmembrane potentials with unique characteristics from cells in the sinus node, in the transition zone between the node and the atrium, in the general region in which the internodal tracts have been described, in Bachmann’s bundle, around the orifice of and within
’ Editorials published by the Journal reflect the views of the authors and do not necessarily represent the views of the Journal or of the American College of Cardiology.
August 1979 The American Journal of CARDIOLOGY Volume 44
385
EDITORIALS
the coronary sinus, in the transition zone between the atrium and the atrioventricular node and in the atrioventricular valves. It often is assumed that the special electric properties somehow are uniquely related to the region from which they are recorded. In this regard, it is troubling to learn that in a single part of the atrium there may be as many as six different cell types, even though six different types of transmembrane action potentials have not been recorded from the same area. There is a clear need for new studies that combine the recording of transmembrane potentials, the measurement of passive electric properties, the marking of cells with defined electric characteristics and the subsequent study of the ultrastructure of the same cells. Some suitable technique such as measurement of the intercellular diffusion of a marker might be included to quantify cell coupling. Specialized Atrial Conduction Tracts One other problem is crystallized by the demonstration that Purkinje-like cells and transitional cells make typical junctions with contractile fibers and that long rows of Purkinje-like cells are not observed. This is the question of the existence of specialized conduction tracts in the mammalian atrium. As Sherf and James emphasize, the problem is not solved by insisting that the criteria established for the His bundle and bundle branches be satisfied by all specialized tracts.5 The ventricular conducting system is one special case. Specialized tracts in the atria may be another. Unfortunately, we do not have good models for predicting the effect on impulse propagation in the heart of an admixture of specialized with nonspecialized cells. It seems
likely that if appropriate assumptions were made concerning cell size and the strength of the action current generated by each single cell, impulse propagation might succeed even if a reasonable proportion of the cells in a bundle of fibers were totally inexcitable. It seems likely also that an appropriate admixture of cells with special properties, such as a more intense fast inward current, would speed propagation in a bundle composed largely of ordinary muscle fibers. This proposal accepts the fact that propagation will always be faster parallel to the fiber bundles than perpendicular to them; however, it also accepts the possibility that in the presence of specialized cells the impulse moves more rapidly than it would in their absence. Once again, suitable studies are needed. Implications Although the paper by Sherf and James1 will elicit quite different reactions from different readers, clearly it is an important communication. It emphasizes how often simplifying assumptions are made in order to try to explain what we would like to be able to explain, and it demonstrates how much we have yet to learn about the complex tissue that constitutes the mammalian atrium. It clearly identifies some of the new studies that are essential before we can come to any general conclusions about where in the atrium arrhythmias may arise, what their mechanism may be and where and how cell structure influences impulse propagation. Finally, we have to face the challenge of the ameboid cell and its consistent relation with P cells. The authors’ suggestions concerning this complex deserve careful experimental evaluation.
References Sherl L, James TN: Fine structure of cells and their histologic organization within the internodal pathways of the heart. Am J Cardiol 44:345-369, 1979 James TN: The connecting pathways between the sinus node and A-V node and between the right and left atrium in the human heart. Am Heart J 66:496-506, 1963 Wagner ML, Lazzara R, Weiss RM, Hoffman BF: Specialized
386
August 1979 The American Journal of CARDIOLOGY
condu.cting fibers in the interatrial band. Circ Res 16502-516, 1966 4. Hogan PM, Davis LD: Evidence for specialized fibers in the canine right atrium. Circ Res 23:367-396, 1966 5. Janse YJ, Anderson RH: Specialized internodal atrial pathways-fact or fiction? Eur J Cardiol 2:117-136, 1974
Volume 44
Fine Structure of Internodal Pathways*
BRIAN New
F. HOFFMAN,
MD
York, New York
In this issue of the Journal, Sherf and James1 provide a morphologic description of six different types of cells in the canine and the human atrium. The data are derived from light and electron microscopic studies on tissues obtained from the parts of the atrium-the Eustachian ridge and Bachmann’s bundle-in which earlier studies by James2 located the anterior and posterior internodal tracts. In addition, the authors consider at some length the possible functional significance of each of the different types of cells in relation to normal and abnormal electric activity. Their paper is certain to provide a new impetus for studies on correlations between structure and function in the mammalian atrium and to add new enthusiasm to the argument about specialized internodal pathways that has been waged periodically since 1910. Specialization of Atrial Cells If, as seems likely, the findings by Sherf and James lead to renewed interest in either topic, a serious effort should be made to avoid some of the problems that have confused the issue over the years. First and foremost, it is essential to have clear definitions that are agreed upon by all concerned. Atria1 cells can be called special or specialized if their properties differ significantly from those of the cells that constitute the bulk of the atria1 myocardium. Evidence of specialization might derive from studies on ultrastructure, electrophysiology or other properties. The morphologic evidence of specialization provided by Sherf and James seems to be clear and compelling. Also, as they note, the cells they studied have a location similar to that described for cells or fibers that were specialized in terms of the characteristics of their transmembrane potentials.“*4 It is From the Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York. Manuscript received May 22, 1979. accepted May 29, 1979. Address for reprints: Brian F. Hoffman, MD, Department of Pharmacology, College of Physicians and Surgeons of Columbia University, 630 West 166 Street, New York, New York 10032.
therefore tempting to assume that one or the other of the morphologically specialized cells they describe corresponds to the electrophysiologically specialized atrial plateau fiber. The authors favor the P cell; others might opt for the Purkinje-like celIs. There is very likely a correlation between structural and functional specialization, but additional studies are essential before one can relate, with certainty, functional characteristics to local differences in structure or ultrastructure. If all other properties were the same, fibers with a small cross-sectional area might be expected to conduct less rapidly than larger fibers. However, if the density of channels for the fast inward current were sufficiently lower in the large than in the small fibers, the converse might be true; at present we do not have methods to make the required measurements. Similarly, because it generally is accepted that a path of low electric resistance between cardiac cells is provided by special properties of the gap or tight junction, it is often assumed that some estilpate of the adequacy of intercellular coupling can be made from measurement of the relative density of such junctions. This may not be correct. It seems likely that a path of reasonably low resistance between cells can be provided by a relatively small number of junctional particles in correct apposition. What is required to evaluate the question is the direct determination of the coupling resistance between cells and, for the same cells, appropriate studies on freeze-fractured gap junctions using quantitative techniques. Electric Properties of Atria1 Cells The studies by Sherf and James present a special problem to the electrophysiologist. By means of intracellular microelectrodes it has been possible to record transmembrane potentials with unique characteristics from cells in the sinus node, in the transition zone between the node and the atrium, in the general region in which the internodal tracts have been described, in Bachmann’s bundle, around the orifice of and within
’ Editorials published by the Journal reflect the views of the authors and do not necessarily represent the views of the Journal or of the American College of Cardiology.
August 1979 The American Journal of CARDIOLOGY Volume 44
385
EDITORIALS
the coronary sinus, in the transition zone between the atrium and the atrioventricular node and in the atrioventricular valves. It often is assumed that the special electric properties somehow are uniquely related to the region from which they are recorded. In this regard, it is troubling to learn that in a single part of the atrium there may be as many as six different cell types, even though six different types of transmembrane action potentials have not been recorded from the same area. There is a clear need for new studies that combine the recording of transmembrane potentials, the measurement of passive electric properties, the marking of cells with defined electric characteristics and the subsequent study of the ultrastructure of the same cells. Some suitable technique such as measurement of the intercellular diffusion of a marker might be included to quantify cell coupling. Specialized Atrial Conduction Tracts One other problem is crystallized by the demonstration that Purkinje-like cells and transitional cells make typical junctions with contractile fibers and that long rows of Purkinje-like cells are not observed. This is the question of the existence of specialized conduction tracts in the mammalian atrium. As Sherf and James emphasize, the problem is not solved by insisting that the criteria established for the His bundle and bundle branches be satisfied by all specialized tracts.5 The ventricular conducting system is one special case. Specialized tracts in the atria may be another. Unfortunately, we do not have good models for predicting the effect on impulse propagation in the heart of an admixture of specialized with nonspecialized cells. It seems
likely that if appropriate assumptions were made concerning cell size and the strength of the action current generated by each single cell, impulse propagation might succeed even if a reasonable proportion of the cells in a bundle of fibers were totally inexcitable. It seems likely also that an appropriate admixture of cells with special properties, such as a more intense fast inward current, would speed propagation in a bundle composed largely of ordinary muscle fibers. This proposal accepts the fact that propagation will always be faster parallel to the fiber bundles than perpendicular to them; however, it also accepts the possibility that in the presence of specialized cells the impulse moves more rapidly than it would in their absence. Once again, suitable studies are needed. Implications Although the paper by Sherf and James1 will elicit quite different reactions from different readers, clearly it is an important communication. It emphasizes how often simplifying assumptions are made in order to try to explain what we would like to be able to explain, and it demonstrates how much we have yet to learn about the complex tissue that constitutes the mammalian atrium. It clearly identifies some of the new studies that are essential before we can come to any general conclusions about where in the atrium arrhythmias may arise, what their mechanism may be and where and how cell structure influences impulse propagation. Finally, we have to face the challenge of the ameboid cell and its consistent relation with P cells. The authors’ suggestions concerning this complex deserve careful experimental evaluation.
References Sherl L, James TN: Fine structure of cells and their histologic organization within the internodal pathways of the heart. Am J Cardiol 44:345-369, 1979 James TN: The connecting pathways between the sinus node and A-V node and between the right and left atrium in the human heart. Am Heart J 66:496-506, 1963 Wagner ML, Lazzara R, Weiss RM, Hoffman BF: Specialized
386
August 1979 The American Journal of CARDIOLOGY
condu.cting fibers in the interatrial band. Circ Res 16502-516, 1966 4. Hogan PM, Davis LD: Evidence for specialized fibers in the canine right atrium. Circ Res 23:367-396, 1966 5. Janse YJ, Anderson RH: Specialized internodal atrial pathways-fact or fiction? Eur J Cardiol 2:117-136, 1974
Volume 44
