Summary
We studied the ultrastructure of the rat carotid body and found that glomus cells (Type I cells) are of two types (A and B) based on the size of their dense-cored vesicles. Dense-cored vesicles in type A cells have a mean diameter nearly 30% larger than those in type B cells. Although we seldom found nerve endings on type B cells, at least two types of nerves end on type A cells. Axonal degeneration studies showed that more than 95% of these nerves are afferent axons which leave the carotid body in the carotid sinus nerve and have their cell bodies in the sensory (petrosal) ganglion of the glossopharyngeal nerve. Less than 5% are preganglionic efferent axons from the cervical sympathetic trunk which enter the carotid body with axons from the superior cervical sympathetic ganglion. We found no efferent axons from the glossopharyngeal nerve which end on glomus cells, although some do end on ganglion cells.
Afferent and efferent nerve endings can be distinguished morphologically, although both types contain many synaptic vesicles and few large dense-cored vesicles. Synaptic vesicles in afferent nerve endings are 15% larger but 60% less numerous than those in efferent nerve endings. Large densecored vesicles in afferent nerve endings are similar in size but 80% less numerous than those in efferent nerve endings. Some regions of afferent nerve endings are presynaptic to glomus cells, some are postsynaptic, and some form reciprocal synapses. Efferent nerve endings are presynaptic to glomus cells but not in synaptic contact with afferent nerve endings.
Blood vessels in the carotid body have both a parasympathetic and a sympathetic innervation. Most parasympathetic vasomotor nerves arise within the carotid body from ganglion cells whose preganglionic innervation is from the glossopharyngeal nerve. Terminals of these vasomotor nerves contain clear-cored synaptic vesicles. Sympathetic vasomotor nerves, most of which come from ganglion cells in the superior cervical ganglion (and from a few ganglion cells in the carotid body) have dense-cored synaptic vesicles.
We postulate that (I) afferent nerve endings, which are interconnected with glomus cells by reciprocal synapses, are chemoreceptors; (2) glomus cells are dopaminergic interneurons which modulate the sensitivity of chemoreceptive nerve endings; (3) glomus cells and afferent nerves interact through reciprocal synapses which form an inhibitory feedback loop: sensory nerves release an excitatory transmitter when stimulated, the transmitter causes glomus cells to release dopamine, and dopamine inhibits the sensory nerves; (4) the feedback loop may contribute to the hyperbolic nature of the curve described by the relationship between arterial oxygen pressure and the rate of chemo-receptor firing; (5) by enhancing dopamine release from some glomus cells, preganglionic sympathetic nerves decrease chemoreceptor activity, an effect opposite from that of vasoconstriction produced by postganglionic sympathetic nerves on blood vessels j (6) synaptic interconnections enable glomus cells to influence one another. We cannot exclude the possibility that glomus cells, like afferent nerve endings, are chemoreceptors sensitive to hypoxia and hypercapnia or that glomus cells, in addition to their other functions, secrete a polypeptide hormone.
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References
Abbott, C. P., Daly, M. De B. andHowe, A. (1972) Early ultrastructural changes in the carotid body after degenerative section of the carotid sinus nerve in the cat.Acta Anatomica 83, 161–85.
Ábrahám, A. (1968) Electron microscopic investigations on the human carotid body (preliminary communication).Zeitschrift für Mikroskopisch-Anatomische Forschung 79, 309–15.
Ábrahám, A. (1969) Elektronenmikroskopische Untersuchungen an menschlichen Karotiskörpern.Zeitschrift für Mikroskopisch-Anatomische Forschung 81, 413–53.
Akert, K., Pfenninger, K., Sandri, C. andMoor, H. (1972) Freeze etching and cytochemistry of vesicles and membrane complexes in synapses of the central nervous system. InStructure and Function of Synapses (edited by Pappas, G. D. and Purpura, D. P.), pp. 67–86. New York: Raven Press.
Al-Lami, F. andMurray, R. G. (1968a) Fine structure of the carotid body of normal and anoxic cats.Anatomical Record 160, 697–718.
Al-Lami, F. andMurray, R. G. (1968b) Fine structure of the carotid body ofMacaca mulata monkey.Journal of Ultrastructure Research 24, 465–78.
Banker, B. Q. andGirvin, J. P. (1971) The ultrastructural features of the mammalian muscle spindle.Journal of Neuropathology and Experimental Neurology 30, 155–95.
Battaglia, G. (1966) Observazioni ultrastrutturali sul glomo carotideo del ratto.Bollettino della Societa Italiana di Biologia Sperimentale 42, 1581–4.
Biscoe, T. J. (1971) Carotid body: Structure and function.Physiological Reviews 51, 437–95.
Biscoe, T. J., Bradley, G. W. andPurves, M. J. (1969) The relation between carotid body chemoreceptor activity and carotid sinus pressure in the cat.Journal of Physiology (London) 203, 40P.
Biscoe, T. J., Lall, A. andSampson, S. R. (1969) On the nerve endings associated with the carotid body glomus cells of the cat.Journal of Physiology (London) 200, 131P-2P.
Biscoe, T. J., Lall, A. andSampson, S. R. (1970) Electron microscopic and electrophysiological studies on the carotid body following intracranial section of the glossopharyngeal nerve.Journal of Physiology (London) 208, 133–52.
Biscoe, T. J. andPallot, D. (1972) Serial reconstruction with the electron microscope of carotid body tissue. The type I cell nerve supply.Experientia (Basel) 28, 33–4.
Biscoe, T. J. andSampson, S. R. (1968) Rhythmical and nonrhythmical spontaneous activity recorded from the central cut end of the sinus nerve.Journal of Physiology (London) 196, 327–38.
Biscoe, T. J. andSilver, A. (1966) The distribution of cholinesterases in the cat carotid body.Journal of Physiology (London) 183, 501–12.
Biscoe, T. J. andStehbens, W. E. (1966) Ultrastructure of the carotid body.Journal of Cell Biology 30, 563–78.
Biscoe, T. J. andStehbens, W. E. (1967) Ultrastructure of the denervated carotid body.Quarterly Journal of Experimental Physiology 52, 31–6.
Blümcke, S., Rode, J. andNiedorf, H. R. (1967) The carotid body after oxygen deficiency.Zeitschrift für Zellforschung und Mikroskopische Anatomie 80, 52–77.
Böck, P., Stockinger, L. andVyslonzil, E. (1970) Die feinstrucktur des Glomus caroticum beim Menschen.Zeitschrift für Zellforschung und Mikroskopische Anatomie 105, 543–68.
Bodian, D. (1962) The generalized vertebrate neuron.Science 137, 323–6.
Bunt, A. H. (1969) Formation of coated and ‘synaptic’ vesicles within neurosecretory axon terminals of the crustacean sinus gland.Journal of Ultrastructure Research 28, 411–21.
Cammermeyer, J. (1962) I. An evaluation of the significance of the ‘dark’ neuron.Ergebnisse der Anatomie und Entwicklungsgeschichte 36, 1–61.
Chen, I-L. andYates, R. D. (1969) Electron microscopic radioautographic studies of the carotid body following injections of labeled biogenic amine precursors.Journal of Cell Biology 42, 794–803.
Chiocchio, S. R., King, M. P., Carballo, L. andAngelakos, E. T. (1971) Monoamines in the carotid body cells of the cat.Journal of Histochemistry and Cytochemistry 19, 621–6.
Coggeshall, R. E. (1971) A possible sensory-motor neuron inAplysia californica.Tissue and Cell 3, 637–47.
Dahlström, A. (1973) Aminergic transmission. Introduction and short review.Brain Research 62, 441–60.
De Castro, F. (1926) Sur la structure et l'innervation de la glande intercarotidienne (glomus caroticum) de l'homme et des mammifères, et sur un nouveau système d'innervation autonome du nerf glossopharyngien.Travaux du Laboratoire de Recherches Biologiques de l'Universitè de Madrid 24, 365–432.
De Castro, F. (1928) Sur la structure et l'innervation du sinus carotidien de l'homme et des mammifères. Nouveaux faits sur l'innervation et la fonction du glomus caroticum.Travaux de Laboratoire de Recherches Biologiques de l'Université de Madrid 25, 330–80.
Douglas, W. W. (1952) The effect of a ganglion-blocking drug, hexamethonium, on the response of the cat's carotid body to various stimuli.Journal of Physiology (London) 118, 373–83.
Dowling, J. E. (1968) Synaptic organization of the frog retina: an electron microscopic analysis comparing the retinas of frogs and primates.Proceedings of the Royal Society of London, Series B 170, 205–28.
Eränkö, O. andHärkönen, M. (1965) Monoamine-containing small cells in the superior cervical ganglion of the rat and an organ composed of them.Acta Physiologica Scandinavica 63, 511–12.
Eyzaguirre, C. andLewin, J. (1961) The effect of sympathetic stimulation on carotid nerve activity.Journal of Physiology (London) 159, 251–67.
Eyzaguirre, C., Nishi, K. andFidone, S. (1972) Chemoreceptor synapses in the carotid body.Federation Proceedings 31, 1385–93.
Fidone, S. J. andSato, A. (1970) Efferent inhibition and antidromic depression of chemoreceptor A-fibers from the cat carotid body.Brain Research 22, 181–93.
Fillenz, M. (1971) Fine structure of noradrenaline storage vesicles in nerve terminals of the ratvasdeferens.Philosophical Transactions of the Royal Society of London, Series B 261, 319–23.
Gillis, D. B. andMitchell, R. A. (1973) Erythropoiesis in carotid body resected cats.Blood 42, 907–12.
Goodman, N. W. (1973) Efferent control of arterial chemoreceptors mediated by glossopharyngeal fibres and artifacts introduced by stimulation techniques.Journal of Physiology (London) 230, 295–311.
Goodman, N. W. andMccloskey, D. I. (1972) Intracellular potentials in the carotid body.Brain Research 39, 501–4.
Grillo, M. A. (1966) Electron microscopy of sympathetic tissues.Pharmacological Reviews 18, 387–99.
Grimley, P. M. andGlenner, G. G. (1968) Ultrastructure of the human carotid body. A perspective on the mode of chemoreception.Circulation 37, 648–65.
Hansen, A. J., Fogh, J., MøllgÅrd, K. andSørensen, S. C. (1973) Evidence against erythropoietin production by the carotid body.Respiration Physiology 18, 101–6.
Hess, A. andZapata, P. (1972) Innervation of the cat carotid body: normal and experimental studies.Federation Proceedings 31, 1365–82.
Heuser, J. E. andReese, T. S. (1973) Evidence for recycling of synaptic vesicle membrane during transmitter release at the frog neuromuscular junction.Journal of Cell Biology 57, 315–44.
Heymans, C., Bouckaert, J. J. andDautrebande, L. (1930) Sinus carotidien et reflexes respiratoires, II. Influences respiratoires réflexes de l'acidose, de l'alcalose, de l'anhydride carbonique, de l'ion hydrogène et de l'anoxémie. Sinus carotidiens et échanges respiratoires dans les poumons et au dela des poumons.Archives Internationales de Pharmacodynamie et de Therapie 39, 400–48.
Hoffmann, H. andBirrell, J. H. W. (1958) The carotid body in normal and anoxic states: an electron microscopic study.Acta Anatomica 32, 297–311.
Höglund, R. (1967) An ultrastructural study of the carotid body of horse and dog.Zeitschrift für Zellforshung und Mikroskopische Anatomie 76, 568–76.
Kobayashi, S. (1968) Fine structure of the carotid body of the dog.Archivum Histologicum Japonicum 30, 95–120.
Kobayashi, S. (1971a) Comparative cytological studies of the carotid body, I. Demonstration of monoamine-storing cells by correlated chromaffm reaction and fluorescence histochemistry.Archivum Histologicum Japonicum 33, 319–39.
Kobayashi, S. (1971b) Comparative cytological studies of the carotid body, 2. Ultrastructure of the synapses on the chief cell.Archivum Histologicum Japonicum 33, 397–420.
Kobayashi, S. andUehara, M. (1970) Occurrence of afferent synaptic complexes in the carotid body of the mouse.Archivum Histologicum Japonicum 32, 193–201.
Kondo, H. (1971) An electron microscopic study on innervation of the carotid body of guinea pig.Journal of Ultrastructure Research 37, 544–62.
Kramer, S. G., Potts, A. M. andMangnall, Y. (1971) Dopamine: A retinal neurotransmitter, II. Autoradiographic localization of H3-dopamine in the retina.Investigative Ophthalmology 10, 617–24.
Landon, D. N. (1972) The fine structure of the equatorial regions of developing muscle spindles in the rat.Journal of Neurocytology I, 189–210.
Laties, A. M. andJacobowitz, D. (1966) A comparative study of the autonomic innervation of the eye in monkey, cat, and rabbit.Anatomical Record 156, 383–96.
Laurent, P. andJager-Barrés, M.-C. (1969) Activité efférent d'origine centrale dans le nerf sinocarotidien du lapin.Journal de Physiologie (Paris) 61, 403–9.
Lenn, N. J. andReese, T. S. (1966) The fine structure of nerve endings in the nucleus of the trapezoid body and the ventral cochlear nucleus.American Journal of Anatomy 118, 375–89.
Lever, J. D., Lewis, P. R. andBoyd, J. D. (1959) Observations on the fine structure and histochemistry of the carotid body in the cat and rabbit.Journal of Anatomy 93, 478–96.
Libet, B. andOwman, C. (1974) Concomitant changes in formaldehyde-induced fluorescence of dopamine interneurones and in slow inhibitory postsynaptic potentials of the rabbit superior cervical ganglion, induced by stimulation of the preganglionic nerve or by a muscarinic agent.Journal of Physiology (London) 237, 635–62.
Martinez, I. R., Jr andPekarthy, J. M. (1974) Ultrastructure of encapsulated nerve endings in rat gingiva (I).American Journal of Anatomy 140, 135–8.
Matthews, M. R. (1971) Evidence from degeneration experiments for the preganglionic origin of afferent fibres to the small granule-containing cells of the rat superior cervical ganglion.Journal of Physiology (London)218, 95P-6P.
Matthews, M. R. andRaisman, G. (1969) The ultrastructure and somatic efferent synapses of small granule-containing cells in the superior cervical ganglion.Journal of Anatomy 105, 255–82.
McDonald, D. M. andMitchell, R. A. (1974) A quantitative analysis of synaptic connections in the rat carotid body. InThe Peripheral Arterial Chemoreceptors (edited by Purves, M. J.), in press. Cambridge: Cambridge University Press.
McDonald, D. M. andRasmussen, G. L. (1971) Ultrastructural characteristics of synaptic endings in the cochlear nucleus having acetylcholinesterase activity.Brain Research 28, 1–18.
Mckenna, O. C. andRosenbluth, J. (1974) Cytological evidence for catecholamine-containing sensory cells bordering the ventricle of the toad hypothalamus.Journal of Comparative Neurology 154, 133–48.
Mills, E. andJöbsis, F. F. (1972) Mitochondrial respiratory chain of carotid body and chemoreceptor response to changes in oxygen tension.Journal of Neurophysiology 35, 405–28.
Mitchell, R. A. andMcDonald, D. M. (1974) Adjustment of chemoreceptor sensitivity in the cat carotid body by reciprocal synapses. InThe Peripheral Arterial Chemoreceptors (edited by Purves, M. J.), in press. Cambridge: Cambridge University Press.
Mitchell, R. A., Sinha, A. K. andMcDonald, D. M. (1972) Chemoreceptive properties of regenerated endings of the carotid sinus nerve.Brain Research 43, 681–5.
Morita, E., Chiocchio, S. R. andTramezzani, J. H. (1969) Four types of main cells in the carotid body of thecat.Journal of Ultrastructure Research 28, 399–410.
Morita, E., Chiocchio, S. R. andTramezzani, J. H. (1970) The carotid body of the Weddell seal (Leptonychotes weddelli).Anatomical Record 167, 309–28.
Munger, B. L. (1971) Patterns of organization of peripheral sensory receptors. InHandbook of Sensory Physiology, Vol. I, Principles of Receptor Physiology (edited by Loewenstein, W. R.), pp. 523–56. Berlin: Springer-Verlag.
Murray, R. G., Murray, A. andFujimoto, S. (1969) Fine structure of gustatory cells in rabbit taste buds.Journal of Ultrastructure Research 27, 444–61.
Nagasawa, J., Douglas, W. W. andSchulz, R. A. (1971) Micropinocytotic origin of coated and smooth microvesicles (‘synaptic vesicles’) in neurosecretory terminals of posterior pituitary glands demonstrated by incorporation of horseradish peroxidase.Nature 232, 341–2.
Neil, E. andO'regan, R. G. (1969) Effects of sinus and aortic nerve efferents on arterial chemoreceptor function.Journal of Physiology (London) 200, 69P-71P.
Neil, E. andO'regan, R. G. (1971a) The effects of electrical stimulation of the distal end of the cut sinus and aortic nerves on peripheral arterial chemoreceptor activity in the cat.Journal of Physiology (London)215, 15–32.
Neil, E. andO'regan, R. G. (1971b) Efferent and afferent impulse activity recorded from few-fibre preparations of otherwise intact sinus and aortic nerves.Journal of Physiology (London)215, 33–47.
Paulo, L. G., Fink, G. D., Roh, B. L. andFisher, J. W. (1973) Influence of carotid body ablation on erythropoietin production in rabbits.American Journal of Physiology 224, 442–4.
Pearse, A. G. E. (1969) The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologie, physiologic and pathologic implications of the concept.Journal of Histochemistry and Cytochemistry 17, 303–13.
Peracchia, C. andMittler, B. S. (1972) Fixation by means of glutaraldehyde-hydrogen peroxide reaction products.Journal of Cell Biology 53, 234–8.
Peters, A., Palay, S. L. andWebster, H. De F. (1970)The Fine Structure of the Nervous System. New York: Harper and Row.
Purves, M. J. (1970) The role of the cervical sympathetic nerve in the regulation of oxygen consumption of the carotid body of the cat.Journal of Physiology (London)209, 417–31.
Ramón Y Cajal, S. (1952)Histologie du Systeme Nerveux de l'Homme et des Vertébrés, Tome I. pp. 722–53. Madrid: Consejo Superior de Investigaciones. Cientificas.
Reese, T. S. andShepherd, G. M. (1972) Dendro-dendritic synapses in the central nervous system. InStructure and Function of Synapses (edited by Pappas, G. D. and Purpura, D. P.), pp. 121–136. New York: Raven Press.
Richardson, K. C. (1962) The fine structure of autonomie nerve endings in smooth muscle of the ratvas deferens.Journal of Anatomy (London)96, 427–42.
Rogers, D. C. (1965) The development of the rat carotid body.Journal of Anatomy (London)99, 89–101.
Sampson, S. R. (1971) Effects of mecamylamine on responses of carotid body chemoreceptorsin vivo to physiological and pharmacological stimuli.Journal of Physiology (London)212, 655–66.
Sampson, S. R. (1972) Mechanism of efferent inhibition of carotid body chemoreceptors in the cat.Brain Research 45, 266–70.
Sampson, S. R. (1974) Pharmacology of feedback inhibition of carotid body chemoreceptors in the cat. InThe Peripheral Arterial Chemoreceptors (edited by Purves, M. J.), in press. Cambridge: Cambridge University Press.
Sampson, S. R. andBiscoe, T. J. (1970) Efferent control of the carotid body chemoreceptor.Experientia (Basel)26, 261–2.
Siegrist, G., Dolivo, M., Dunant, Y., Foroglou-Kerameus, C., De Ribaupierre, F. andRouiller, C. (1968) Ultrastructure and function of the chromaffin cells in the superior cervical ganglion of the rat.Journal of Ultrastructure Research 25, 381–407.
Smith, C. (1924) The origin and development of the carotid body.American Journal of Anatomy 34, 87–131.
Smith, C. A. andRasmussen, G. L. (1965) Degeneration in the efferent nerve endings in the cochlea after axonal section.Journal of Cell Biology 26, 63–77.
Snedecor, G. W. andCochran, W. G. (1967)Statistical Methods, pp. 115–16. Ames, Iowa: Iowa State University Press.
Thoenen, H. andTranzer, J. P. (1971) Functional importance of subcellular distribution of false adrenergic transmitters.Progress in Brain Research 34, 223–36.
Thoenen, H., Tranzer, J. P., Hürlimann, A. andHaefely, W. (1966) Untersuchungen zur Frage eines cholinergischen Gliedes in der postganglionären sympathischen Transmission.Helvetica Physiologica et Pharmacologica Acta 24, 229–46.
Tramezzani, J. H., Morita, E. andChiocchio, S. R. (1971) The carotid body as a neuroendocrine organ involved in control of erythropoiesis.Proceedings of the National Academy of Science 68, 52–5.
Tranzer, J. P. andRichards, J. G. (1971) Fine structural aspects of the effect of 6-hydroxydopamine on peripheral adrenergic neurons. In6-Hydroxydopamine and Catecholamine Neurons (edited by Malmfors, T. and Thoenen, H., pp. 15–31. New York: American Elsevier Publishing Company; Amsterdam, London: North-Holland Publishing Company.
Verna, A. (1971) Infrastructure des divers types de terminaisons nerveuses dans le glomus carotidien du lapin.Journal de Microscopie 10, 59–66.
Verna, A. (1973) Terminaisons nerveuses afférentes et efférentes dans le glomus carotidien du lapin.Journal de Microscopie 16, 299–308.
Westfall, J. A. (1973) Ultrastructural evidence for a granule-containing sensory-motor-interneuron inHydra littoralis.Journal of Ultrastructure Research 42, 268–82.
Williams, T. H. andPalay, S. L. (1969) Ultrastructure of the small neurons in the superior cervical ganglion.Brain Research 15, 17–34.
Willshaw, P. (1974) Sinus nerve efferent fibres as a link between central and peripheral chemoreceptors. InThe Peripheral Arterial Chemoreceptors (edited by Purves, M. J.), in press. Cambridge: Cambridge University Press.
Yates, R. D., Chen, I.-L. andDuncan, D. (1970) Effects of sinus nerve stimulation on carotid body glomus cells.Journal of Cell Biology 46, 544–52.
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McDonald, D.M., Mitchell, R.A. The innervation of glomus cells, ganglion cells and blood vessels in the rat carotid body: A quantitative ultrastructural analysis. J Neurocytol 4, 177–230 (1975). https://doi.org/10.1007/BF01098781
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DOI: https://doi.org/10.1007/BF01098781