The mammalian sinoatrial node

SummaryThe sinoatrial node (SAN) was discovered in 1906 by Keith and Flack. The relation between its ultrastructure and function was first studied by Trautwein and Uchizono in 1963, whereas this relation was definitely established by Taylor and coworkers in 1978.The impulse originates from cells with a relatively low percentage of myofilaments. Earliest discharge is restricted to one site only in rabbit, guinea pig, cat, and pig and presumably also in larger animals. From this primary pacemaker area, the impulse is preferentially conducted towards the crista terminalis. The amount of cells in the primary pacemaker area may vary from a few hundred to a few thousand. In rabbit, guinea pig, cat, and pig, the amount of collagen is considerable. Normal SAN function was observed in the cat although the SAN volume occupied by myocytes was less than 5%. Changes in ionic composition of the perfusion fluid and the addition of autonomic substances may cause pacemaker shifts and altered activation patterns.

[1]  P. Savard,et al.  Vagal effects on sinoatrial and atrial conduction studied with epicardial mapping in dogs: the influence of pacemaker shifts on the measurement of sinoatrial conduction time. , 1985, Canadian journal of physiology and pharmacology.

[2]  H. Brown,et al.  How does adrenaline accelerate the heart? , 1979, Nature.

[3]  D. Goodenough.  In vitro formation of gap junction vesicles , 1976, The Journal of cell biology.

[4]  G. Rozanski,et al.  Electrophysiology of functional subsidiary pacemakers in canine right atrium. , 1985, The American journal of physiology.

[5]  K. R. Anderson,et al.  Location and vascular supply of sinus node in human heart. , 1979, British heart journal.

[6]  E. R. Pavlovich,et al.  Morphometric detection of specialized internodal conducting pathways of the heart , 1981, Bulletin of Experimental Biology and Medicine.

[7]  A. Noma,et al.  On the kinetics of the potassium channel activated by acetylcholine in the S-A node of the rabbit heart , 1980, Pflügers Archiv.

[8]  A. Keith.  THE SINO-AURICULAR NODE: A HISTORICAL NOTE , 1942, British heart journal.

[9]  S. Weidmann,et al.  Cardiac resting and action potentials recorded with an intracellular electrode , 1951, The Journal of physiology.

[10]  J. J. Taylor,et al.  The pacemaker cell of the sinoatrial node of the rabbit. , 1978, The American journal of physiology.

[11]  Vonk Jt.  Sick sinus syndrome , 1979 .

[12]  A. Noma,et al.  Inward current of the rabbit sinoatrial node cell , 1977, Pflügers Archiv.

[13]  P. Åstrand,et al.  Textbook of Work Physiology , 1970 .

[14]  T. N. James,et al.  Electrical Activity in canine sinus node cells during arrest produced by acetylcholine. , 1981, Journal of molecular and cellular cardiology.

[15]  E. Carafoli.  The homeostasis of calcium in heart cells. , 1985, Journal of molecular and cellular cardiology.

[16]  E. Gang,et al.  Hemodynamic influences on sinus node recovery time: effects of autonomic blockade. , 1986, Journal of the American College of Cardiology.

[17]  D. Escande,et al.  Age-related changes of action potential plateau shape in isolated human atrial fibers. , 1985, The American journal of physiology.

[18]  A. Wilde,et al.  The Combined Effects of Hypoxia, High K+, and Acidosis on the Intracellular Sodium Activity and Resting Potential in Guinea Pig Papillary Muscle , 1986, Circulation research.

[19]  D. Noble,et al.  Relationship between the transient inward current and slow inward currents in the sino‐atrial node of the rabbit. , 1986, The Journal of physiology.

[20]  J. Balachander,et al.  Sinus node function after autonomic blockade in normals and in sick sinus syndrome. , 1984, International journal of cardiology.

[21]  S. Bishop,et al.  Morphology of the specialized conducting tissue in the atria of the equine heart , 1967, The Anatomical record.

[22]  Yoshihisa Kurachi,et al.  Action potential and membrane currents of single pacemaker cells of the rabbit heart , 1984, Pflügers Archiv.

[23]  F. I. Bonke.  The Sinus Node , 1978, Springer Netherlands.

[24]  Y. Sugi,et al.  Freeze-fracture studies of the sinoatrial and atrioventricular nodes of the caprine heart, with special reference to the nexus , 2004, Cell and Tissue Research.

[25]  G. Noseda,et al.  [Familial bradycardia: a family with sick sinus and atrioventricular block]. , 1979, Schweizerische medizinische Wochenschrift.

[26]  R. Winkle,et al.  The electrophysiologic effects of quinidine in the transplanted human heart. , 1977, The Journal of clinical investigation.

[27]  W. Giles,et al.  A transient outward current in isolated cells from the crista terminalis of rabbit heart. , 1985, The Journal of physiology.

[28]  M. Sparrow,et al.  Inhibition of cycling and noncycling cross bridges in skinned smooth muscle by vanadate. , 1986, The American journal of physiology.

[29]  正岡 佳子,et al.  薬剤投与によりsinus node dysfunctionが誘発されたWPW症候群の1例 : 日本循環器学会第40回中国・四国地方会 , 1983 .

[30]  D. Glomset,et al.  A morphologic study of the cardiac conduction system in ungulates, dog, and man: Part I: The sinoatrial node , 1940 .

[31]  M. Bertrand,et al.  Complete denervation of the heart (autotransplantation) for treatment of severe, refractory coronary spasm. , 1981, The American journal of cardiology.

[32]  M. Vassalle,et al.  Dual excitatory channels in the sinus node. , 1978, Journal of molecular and cellular cardiology.

[33]  B. Lüderitz,et al.  Comparison between intracellular and extracellular direct current recordings of sinus node activity for evaluation of sinoatrial conduction time. , 1984, Circulation.

[34]  A E Becker,et al.  Functional and Morphological Organization of the Rabbit Sinus Node , 1980, Circulation research.

[35]  O. Langendorff,et al.  Untersuchungen am überlebenden Säugethierherzen , 1895, Archiv für die gesamte Physiologie des Menschen und der Tiere.

[36]  W. C. Randall,et al.  Comparison of SA nodal and subsidiary atrial pacemaker function and location in the dog. , 1978, The American journal of physiology.

[37]  J. Talano,et al.  Current concepts in sick sinus syndrome. I. Anatomy, physiology, and pharmacologic causes. , 1985, Archives of internal medicine.

[38]  E. Seifen.  Dependency on Mg-and Ca-concentration of cycle length in spontaneously beating guinea-pig atria , 2004, Pflügers Archiv.

[39]  R. Vaughan-Jones.  Non‐passive chloride distribution in mammalian heart muscle: micro‐electrode measurement of the intracellular chloride activity. , 1979, The Journal of physiology.

[40]  M. M. Black,et al.  Unusual manifestations of severe sick sinus syndrome. , 1980, American heart journal.

[41]  J. Spear,et al.  The Effect of Brief Vagal Stimulation on the Isolated Rabbit Sinus Node , 1979, Circulation research.

[42]  H. Jongsma,et al.  Pacemaker cell types in the rabbit sinus node: a correlative ultrastructural and electrophysiological study. , 1984, Journal of molecular and cellular cardiology.

[43]  W. Mandel,et al.  Studies on the Mechanism of Sinus Node Dysfunction in the Sick Sinus Syndrome , 1978, Circulation.

[44]  M. Lev.  Aging changes in the human sinoatrial node. , 1954, Journal of gerontology.

[45]  H. Kulbertus,et al.  Histopathological correlates of sinoatrial disease. , 1978, British heart journal.

[46]  J. Linhart,et al.  A New Method for Measurement of Sinoatrial Conduction Time , 1978, Circulation.

[47]  C. Manjunath,et al.  Cell biology and protein composition of cardiac gap junctions. , 1985, The American journal of physiology.

[48]  T. N. James,et al.  Comparative Ultrastructure of the Sinus Node in Man and Dog , 1966, Circulation.

[49]  W. C. Randall,et al.  Cardiac Arrhythmias in the Conscious Dog After Excision of the Sinoatrial Node and Crista Terminalis , 1979, Circulation.

[50]  H. Brown.  Electrophysiology of the sinoatrial node. , 1982, Physiological reviews.

[51]  H. Jongsma,et al.  Functional and morphological organization of the guinea-pig sinoatrial node compared with the rabbit sinoatrial node. , 1985, Journal of molecular and cellular cardiology.

[52]  J. Boineau,et al.  Quantitative relation between sites of atrial impulse origin and cycle length. , 1983, The American journal of physiology.

[53]  F. Bowman,et al.  Methods for Recording Electrograms of the Sinoatrial Node During Cardiac Surgery in Man , 1980, Circulation.

[54]  H. Strauss,et al.  The Estimation of Sinoatrial Conduction Time in Rabbit Heart by the Constant Atrial Pacing Technique , 1979, Circulation.

[55]  D. Noble.  The initiation of the heartbeat , 1975 .

[56]  E. Carmeliet,et al.  Chloride ions and the membrane potential of Purkinje fibres , 1961, The Journal of physiology.

[57]  Wolfgang Trautwein,et al.  On The Mechanism of Spontaneous Impulse Generation in the Pacemaker of the Heart , 1961, The Journal of general physiology.

[58]  T. N. James,et al.  Anatomy of the sinus node of the dog , 1962, The Anatomical record.

[59]  H. Jongsma,et al.  Cycle length dependence of the chronotropic effects of adrenaline and acetylcholine in the rabbit sinoatrial node. , 1983, Journal of the autonomic nervous system.

[60]  T. N. James,et al.  Spontaneous Action Potentials of Cells in the Canine Sinus Node , 1976, Circulation research.

[61]  C. Brooks,et al.  The sinoatrial pacemaker of the heart , 1972 .

[62]  I. Zs.-Nagy,et al.  A membrane hypothesis of aging. , 1978, Journal of theoretical biology.

[63]  E. Gordon.  William Harvey and the circulation of the blood. , 1991, Southern medical journal.

[64]  W. C. Randall,et al.  Functional Characteristics of Sinoatrial and Subsidiary Pacemaker Activity in the Canine Right Atrium , 1983, Circulation.

[65]  D. Spray,et al.  Regulation of gap junctional conductance. , 1985, The American journal of physiology.

[66]  B. Lüderitz,et al.  Effects of atrial pacing on atrio-sinus conduction and overdrive suppression in the isolated rabbit sinus node. , 1980, Circulation research.

[67]  D. Noble,et al.  The surprising heart: a review of recent progress in cardiac electrophysiology. , 1984, The Journal of physiology.

[68]  A. Porte,et al.  The fine structure of the conducting system of the monkey heart (Macaca mulatta) , 1973, Zeitschrift für Zellforschung und Mikroskopische Anatomie.

[69]  A. Rein,et al.  Symptomatic sinus bradycardia in infants with structurally normal hearts. , 1985, The Journal of pediatrics.

[70]  A. Romer.  The vertebrate body , 1971 .

[71]  H. Jongsma,et al.  Structure and function of the sino-atrial node: a review. , 1986, European heart journal.

[72]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1952, The Journal of physiology.

[73]  W. Trautwein,et al.  [Membrane and action potentials of single myocardial fibers of cold and warmblooded animals]. , 1952, Pflugers Archiv fur die gesamte Physiologie des Menschen und der Tiere.

[74]  野間 昭典,et al.  Effects of Na+ and K+ on the resting membrane potential of the rabbit sinoatrial node cell , 1975 .

[75]  W. Bleeker,et al.  Temperature dependence of the chronotropic actions of calcium: functional inhomogeneity of the rabbit sinus node. , 1980, Journal of molecular and cellular cardiology.

[76]  F. I. Bonke,et al.  Pacemaker shift in the sino-atrial node during vagal stimulation , 2004, Pflügers Archiv.

[77]  W. Loewenstein,et al.  Junctional intercellular communication: the cell-to-cell membrane channel. , 1981, Physiological reviews.

[78]  T. C. West,et al.  Interaction between Na, Ca, Mg, and vagal stimulation in the S-A node of the rabbit. , 1967, The American journal of physiology.

[79]  H. Lehmann,et al.  Familial sinus node dysfunction with autosomal dominant inheritance. , 1978, British heart journal.

[80]  H. Jongsma,et al.  Little-excitable transitional cells in the rabbit sinoatrial node: a statistical, morphological and electrophysiological study , 1983, Experientia.

[81]  H. Jongsma,et al.  Functional and morphological organization of the cat sinoatrial node. , 1986, Journal of molecular and cellular cardiology.

[82]  G. Marmont.  Studies on the axon membrane; a new method. , 1949, Journal of cellular and comparative physiology.

[83]  D. Chamberlain,et al.  Sinus node disease affecting both parents and both children. , 1979, European journal of cardiology.

[84]  M. Mazzanti,et al.  Properties of the hyperpolarizing‐activated current (if) in cells isolated from the rabbit sino‐atrial node. , 1986, The Journal of physiology.

[85]  D. Chesnoy-Marchais.  Characterization of a chloride conductance activated by hyperpolarization in Aplysia neurones. , 1983, The Journal of physiology.

[86]  H. Brown,et al.  The Relative Contributions of Various Time-Dependent Membrane Currents to Pacemaker Activity in the Sino Atrial Node , 1982 .

[87]  J Tranum-Jensen,et al.  Whole-mount demonstration of cholinesterase-containing nerves in the right atrial wall, nodal tissue, and atrioventricular bundle of the pig heart. , 1971, Journal of anatomy.

[88]  T. N. James,et al.  The sinus node. , 1977, The American journal of cardiology.

[89]  G. Colborn,et al.  Electron microscopy of the sinoatrial node of the squirrel monkey Saimiri sciureus. , 1972, Journal of molecular and cellular cardiology.

[90]  G. Kelliher,et al.  Electrophysiological changes in the rat atrium with age. , 1974, The American journal of physiology.

[91]  S. Rahimtoola,et al.  Characterisation of heart rate response to exercise in the sick sinus syndrome. , 1978, British heart journal.

[92]  G. Goings,et al.  Isolation and protein composition of gap junctions from rabbit hearts. , 1982, The Biochemical journal.

[93]  Two electrophysiologically distinct types of cultured pacemaker cells from rabbit sinoatrial node. , 1986, The American journal of physiology.

[94]  E. Bozler.  THE INITIATION OF IMPULSES IN CARDIAC MUSCLE , 1943 .

[95]  D. Gros,et al.  The Plasma Membrane of Leading Pacemaker Cells in the Rabbit Sinus Node: A Qualitative and Quantitative Ultrastructural Analysis , 1979, Circulation research.

[96]  A. Noma,et al.  The effect of sodium ion on the initial phase of the sinoatrial pacemaker action potentials in rabbits. , 1974, The Japanese journal of physiology.

[97]  J. Titus,et al.  Normal Anatomy of the Human Cardiac Conduction System , 1973, Mayo Clinic proceedings.

[98]  W. J. Meek,et al.  EXPERIMENTS ON THE ORIGIN AND PROPAGATION OF THE IMPULSE IN THE HEART: IV. The Effect of Vagal Stimulation and of Cooling on the Location of the Pacemaker within the Sino-auricular Node , 1914 .

[99]  A. Onat.  Familial sinus node disease and degenerative myopia—a new hereditary syndrome? , 1986, Human Genetics.

[100]  M. Taylor,et al.  Reconstruction of the human sinoatrial node , 1967, The Anatomical record.

[101]  H. Jongsma,et al.  Interaction of Adrenaline and Acetylcholine on Sinus Node Function , 1982 .

[102]  H. Strauss,et al.  Intracellular Potassium Activity in Rabbit Sinoatrial Node: Evaluation during Spontaneous Activity and Arrest , 1982, Circulation research.

[103]  H H Lu,et al.  Shifts in Pacemaker Dominance within the Sinoatrial Region of Cat and Rabbit Hearts Resulting from Increase of Extracellular Potassium , 1970, Circulation research.

[104]  R. Orkand,et al.  Heart Action Potential: Dependence on External Calcium and Sodium Ions , 1964, Science.

[105]  A. Camm,et al.  Sinoatrial function after cardiac transplantation. , 1984, Journal of the American College of Cardiology.

[106]  R. Hariman,et al.  Electrical Activity from the Sinus Node Region in Conscious Dogs , 1980, Circulation research.

[107]  Navaratnam,et al.  The T-tubule system in the specialized and general myocardium of the rat. , 1978, Journal of Anatomy.

[108]  A Keith,et al.  The Form and Nature of the Muscular Connections between the Primary Divisions of the Vertebrate Heart. , 1907, Journal of anatomy and physiology.

[109]  F. Abboud,et al.  Distribution of Coronary Artery Flow to the Canine Right Atrium and Sinoatrial Node , 1977, Circulation research.

[110]  T. C. West,et al.  Ultramicroelectrode recording from the cardiac pacemaker. , 1955, The Journal of pharmacology and experimental therapeutics.

[111]  R W GERARD,et al.  The normal membrane potential of frog sartorius fibers. , 1949, Journal of cellular and comparative physiology.

[112]  H. Jongsma,et al.  Cycle length dependence of the chronotropic effects of adrenaline, acetylcholine, Ca2+ and Mg2+ in the Guinea-pig sinoatrial node. , 1984, Journal of the autonomic nervous system.

[113]  D. DiFrancesco.  The cardiac hyperpolarizing-activated current, if. Origins and developments. , 1985, Progress in biophysics and molecular biology.

[114]  W. C. Randall,et al.  Sinus node dysfunction. An overview with emphasis on autonomic and pharmacologic consideration. , 1978, The American journal of medicine.

[115]  F. Verdonck,et al.  Reduction of potassium permeability by chloride substitution in cardiac cells. , 1977, The Journal of physiology.

[116]  R B Schuessler,et al.  Widespread distribution and rate differentiation of the atrial pacemaker complex. , 1980, The American journal of physiology.

[117]  H. Schaer.  Antagonistische Wirkungen von Magnesium-, Calcium-und Natriumionen auf die Impulsbildung im Sinusknoten des Meerschweinchenherzens , 1968, Pflüger's Archiv für die gesamte Physiologie des Menschen und der Tiere.

[118]  N Toda,et al.  The influence of sympathetic stimulation on transmembrane potentials in the S-A node. , 1968, The Journal of pharmacology and experimental therapeutics.

[119]  D. Noble,et al.  Anion conductance of cardiac muscle , 1961, The Journal of physiology.

[120]  Robertson Jd.  THE OCCURRENCE OF A SUBUNIT PATTERN IN THE UNIT MEMBRANES OF CLUB ENDINGS IN MAUTHNER CELL SYNAPSES IN GOLDFISH BRAINS , 1963 .

[121]  H. Jongsma,et al.  Interaction of adrenaline and acetylcholine on cardiac pacemaker function. Functional inhomogeneity of the rabbit sinus node. , 1980, The Journal of pharmacology and experimental therapeutics.

[122]  W. Trautwein,et al.  The time course of the muscarinic response to ionophoretic acetylcholine application to the S-A node of the rabbit heart , 1981, Pflügers Archiv.

[123]  P. Rakovec.  Method for recording electrical activity of the sinoatrial node in human subjects. , 1981, The American journal of cardiology.

[124]  K. Uchizono,et al.  Electron microscopic and electrophysiologic study of the pacemaker in the sino-atrial node of the rabbit heart , 1963, Zeitschrift für Zellforschung und Mikroskopische Anatomie.

[125]  K. Hayashi.  An electron microscope study on the conduction system of the cow heart. , 1962, Japanese circulation journal.

[126]  G. Zampighi,et al.  Structure of the junction between communicating cells , 1980, Nature.

[127]  M. Flack.  An investigation of the sino‐auricular node of the mammalian heart , 1910, The Journal of physiology.

[128]  J. Tranum-Jensen,et al.  The Fine Structure of the Atrial and Atrioventricular (AV) Junctional Specialized Tissues of the Rabbit Heart , 1978 .

[129]  K. Rosen,et al.  Chronic nonparoxysmal sinus tachycardia in otherwise healthy persons. , 1979, Annals of internal medicine.

[130]  H. Jongsma,et al.  Asymmetry of the sino-atrial conduction in the rabbit heart. , 1982, Journal of molecular and cellular cardiology.

[131]  E. Ling,et al.  An ultrastructural study of the effects of right cervical sympathectomy on the sinuatrial and atrioventricular nodes in the heart of the monkey (Macaca fascicularis). , 1984, Journal of anatomy.

[132]  H. Irisawa.  Comparative physiology of the cardiac pacemaker mechanism. , 1978, Physiological reviews.

[133]  B. Massie,et al.  Electrophysiologic Effects of Combined Autonomic Blockade in Patients with Sinus Node Disease , 1981, Circulation.

[134]  F. Prieto,et al.  Heart-hand syndrome , 2004, Human Genetics.

[135]  M. Sugiura,et al.  A clinicopathologic study on sick sinus syndrome with histological approach to the sinoatrial node. , 1980, Japanese circulation journal.

[136]  A. Noma,et al.  Kinetics and magnitude of the time-dependent potassium current in the rabbit sinoatrial node , 1979, Pflügers Archiv.

[137]  Akinori Noma,et al.  Pacemaker Mechanisms of Rabbit Sinoatrial Node Cells , 1982 .

[138]  S. Kikuchi.  The structure and innervation of the sinu-atrial node of the mole heart , 1976, Cell and Tissue Research.

[139]  T. Bashour.  Classificaion of sinus node dysfunction , 1985 .

[140]  R. Hariman,et al.  Electrograms from the canine sinoatrial pacemaker recorded in vitro and in situ. , 1978, The American journal of cardiology.

[141]  A. Noma,et al.  Does the “pacemaker current” generate the diastolic depolarization in the rabbit SA node cells? , 1983, Pflügers Archiv.

[142]  T. N. James,et al.  Anatomy of the human sinus node , 1961, The Anatomical record.

[143]  K. Rosen,et al.  The anatomic substrate for the sick sinus syndrome in adolescence. , 1980, The American journal of cardiology.

[144]  J. A. E. Eyster,et al.  THE ORIGIN AND CONDUCTION OF THE HEART BEAT , 1921 .

[145]  J. Bigger,et al.  Premature Atrial Stimulation as a Key to the Understanding of Sinoatrial Conduction in Man: Presentation of Data and Critical Review of the Literature , 1973, Circulation.

[146]  J. Houtkooper,et al.  Dependence of the chronotropic effects of calcium, magnesium and sodium on temperature and cycle length in isolated rabbit atria. , 1980, The Journal of pharmacology and experimental therapeutics.

[147]  A. F. Mackintosh.  Sinuatrial disease in young people. , 1981, British heart journal.

[148]  H. Jongsma,et al.  On the Intrinsic Cardiac Rhythm , 1982 .

[149]  J. Talano,et al.  Current concepts in sick sinus syndrome. II. ECG manifestation and diagnostic and therapeutic approaches. , 1985, Archives of internal medicine.

[150]  D. DiFrancesco,et al.  Properties of the current if in the sino‐atrial node of the rabbit compared with those of the current iK, in Purkinje fibres. , 1980, The Journal of physiology.

[151]  K. Matsunuma,et al.  Altered autonomic mechanisms in the sick sinus syndrome and diurnal variations in the parameters of sinus node function. , 1980, Japanese circulation journal.

[152]  M. Kyriakidis,et al.  Sinus node coronary arteries studied with angiography. , 1983, The American journal of cardiology.

[153]  H. Jongsma,et al.  Differences between rabbit sinoatrial pacemakers in their response to Mg, Ca and temperature. , 1983, Cardiovascular research.