Electron microscopic and electrophysiological studies on the carotid body following intracranial section of the glossopharyngeal nerve.
TL;DR: The innervation of carotid body Type I cells has been investigated in seventeen cats at a sterile operation and the glossopharyngeal and vagus nerve roots were cut intracranially on one side.
Abstract: 1. The innervation of carotid body Type I cells has been investigated in seventeen cats. At a sterile operation the glossopharyngeal and vagus nerve roots were cut intracranially on one side.
2. From 1½ to 378 days after the operation the carotid bodies were fixed in situ and prepared for electron microscopy. Nerve endings on Type I cells were found to degenerate with a prolonged time course. In each cat there was a decrease in the number of nerve endings on the operated side as compared with the non-operated side.
3. Before the carotid bodies were fixed, recordings were made from chemoreceptor, and baroreceptor, afferent fibres in the sinus nerve on the operated side. The chemoreceptors responded in the usual way to changes in arterial O2, CO2 and pH; the injection of cyanide evoked a brisk response.
4. It is concluded that the nerve endings on Type I cells are efferent rather than afferent and the cell bodies of their axons are probably in the brain stem.
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TL;DR: The goal of this article is to provide a comprehensive review of current concepts on sensory transduction and transmission of the hypoxic stimulus at the carotid body with an emphasis on integrating cellular mechanisms with the whole organ responses and highlighting the gaps or discrepancies in knowledge.
Abstract: The discovery of the sensory nature of the carotid body dates back to the beginning of the 20th century. Following these seminal discoveries, research into carotid body mechanisms moved forward progressively through the 20th century, with many descriptions of the ultrastructure of the organ and stimulus-response measurements at the level of the whole organ. The later part of 20th century witnessed the first descriptions of the cellular responses and electrophysiology of isolated and cultured type I and type II cells, and there now exist a number of testable hypotheses of chemotransduction. The goal of this article is to provide a comprehensive review of current concepts on sensory transduction and transmission of the hypoxic stimulus at the carotid body with an emphasis on integrating cellular mechanisms with the whole organ responses and highlighting the gaps or discrepancies in our knowledge. It is increasingly evident that in addition to hypoxia, the carotid body responds to a wide variety of blood-borne stimuli, including reduced glucose and immune-related cytokines and we therefore also consider the evidence for a polymodal function of the carotid body and its implications. It is clear that the sensory function of the carotid body exhibits considerable plasticity in response to the chronic perturbations in environmental O2 that is associated with many physiological and pathological conditions. The mechanisms and consequences of carotid body plasticity in health and disease are discussed in the final sections of this article.
453 citations
TL;DR: The ultrastructure of the rat carotid body is studied to postulate that afferent nerve endings, which are interconnected with glomus cells by reciprocal synapses, are chemoreceptors and glomUS cells are dopaminergic interneurons which modulate the sensitivity of chemoreceptive nerve endings.
Abstract: 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.
359 citations
TL;DR: The sections in this article are: General Anatomy, Histology, and Embryology of Carotid Body, Chemoreceptors, Mechanisms of Chemoreception, and Role of Putative Neurotransmitters in Chemotransduction.
Abstract: The sections in this article are:
1
Structure
1.1
General Anatomy, Histology, and Embryology of Carotid Body
1.2
Carotid Body Ultrastructure
1.3
Pathological Changes and Physiologically Induced Changes in Carotid Body Morphology
2
Response of Chemoreceptors
2.1
Resting Chemoreceptor Discharge
2.2
Chemoreceptor Response to Hypoxia
2.3
Chemoreceptor Response to Partial Pressure of CO2 and pH
2.4
Chemoreceptor Response to Temperature and Osmolarity
2.5
Carotid Body Blood Flow, O2 Consumption, and Chemoresponse
2.6
Efferent Modulation of Chemosensory Discharge
3
Mechanisms of Chemoreception
3.1
Transducer Element(s) in Carotid Body
3.2
Biophysical Aspects of Chemoreception
3.3
Role of Putative Neurotransmitters in Chemotransduction
3.4
Hypotheses on Mechanisms of Chemoreception
4
Addendum
4.1
Recent Advances in Carotid Body Chemoreception
4.2
Structure
4.3
Response of Chemoreceptors
4.4
Mechanisms of Chemoreception
242 citations
TL;DR: Developments in several laboratories over the last ∼20 years, aided by the development of a co‐culture model of the rat CB, have shed light on the role of neurotransmitters and neuromodulators in shaping the afferent response and are contributed to current understanding of information processing at CB chemoreceptors.
Abstract: The control of breathing depends critically on sensory inputs to the central pattern generator of the brainstem, arising from peripheral arterial chemoreceptors located principally in the carotid bodies (CBs). The CB receptors, i.e. glomus or type I cells, are excited by chemical stimuli in arterial blood, particularly hypoxia, hypercapnia, acidosis and low glucose, which initiate corrective reflex cardiorespiratory and cardiovascular adjustments. Type I cells occur in clusters and are innervated by petrosal afferent fibres. Synaptic specializations (both chemical and electrical) occur between type I cells and petrosal terminals, and between neighbouring type I cells. This, together with the presence of a wide array of neurotransmitters and neuromodulators linked to both ionotropic and metabotropic receptors, allows for a complex modulation of CB sensory output. Studies in several laboratories over the last 20 years have provided much insight into the transduction mechanisms. More recent studies, aided by the development of a co-culture model of the rat CB, have shed light on the role of neurotransmitters and neuromodulators in shaping the afferent response. This review highlights some of these developments, which have contributed to our current understanding of information processing at CB chemoreceptors.
168 citations
Cites background from "Electron microscopic and electrophy..."
...The idea of an efferent inhibitory pathway to the CB arose in the early 1970s, though the underlying mechanisms were unknown and even controversial (Biscoe et al. 1970; Neil & O’Regan, 1971)....
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References
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TL;DR: Epoxy embedding methods of Glauert and Kushida have been modified so as to yield rapid, reproducible, and convenientembedding methods for electron microscopy.
Abstract: Epoxy embedding methods of Glauert and Kushida have been modified so as to yield rapid, reproducible, and convenient embedding methods for electron microscopy. The sections are robust and tissue damage is less than with methacrylate embedding.
9,741 citations
TL;DR: This communication reports the use of a commercially available lead citratO to eliminate the lead citrate stain in electron microscopy.
Abstract: A disadvantage of the lead strains used in electron microscopy is the amount of time required for their preparation. One of the more stable and reliable stains, commonly called the lead citrate stain or Reynolds' stain (Reynolds, 1963), is made by mixing lead nitrate and sodium citrate in distilled water, allowing time for lead citrate to form, then adding sodium hydroxide to raise the pH of the solution to 12. This communication reports the use of a commercially available lead citratO to eliminate the
4,496 citations
TL;DR: In this article, an experiment may be regarded as forming an individual of a population of experiments which might be performed under the same conditions, and a series of experiments is a sample drawn from this population.
Abstract: Any experiment may be regarded as forming an individual of a “population” of experiments which might be performed under the same conditions. A series of experiments is a sample drawn from this population.
3,222 citations
TL;DR: Fixation experiments with buffered OsO4 solutions have shown that the appearance of the fixed cells is conditioned by the pH of the fixative, and the quality of fixation can be materially improved by buffering the OsO 4 solutions at pH 7.3-7.5 with acetate-veronal buffer.
Abstract: Osmium tetroxide fixation of tissue blocks, as usually effected, is preceded by an acidification of the tissue. This acidification is probably responsible for morphological alterations which are notably disturbing in electron microscopy. The acidification and the resulting morphological alterations cannot be prevented by homogenizing the tissue directly in OsO4 solutions or by adding enzyme inhibitors (fluoride, iodoscetamide) to the fixative. Fixation experiments with buffered OsO4 solutions have shown that the appearance of the fixed cells is conditioned by the pH of the fixative. The quality of fixation can be materially improved by buffering the OsO4 solutions at pH 7.3-7.5, The acetate-veronal buffer appeared to be the most favorable of the buffers tested, Because of these findings, 1 per cent OsO4 buffered at pH 7.3-7.5 with acetate-veronal buffer is recommended as an appropriate fixative for electron microscopy.
2,815 citations
TL;DR: The nucleoids of Escherichia coli are shown to be preserved as a fine-stranded fibrillar nucleoplasm by an OsO4 fixation under defined conditions: acetate-veronal buffer pH 6, presence of Ca++ and amino acids, stabilization with uranyl-acetate before dehydration.
Abstract: The nucleoids of Escherichia coli, independently of the physiological state of the bacteria, are shown to be preserved as a fine-stranded fibrillar nucleoplasm by an OsO(4) fixation under defined conditions: acetate-veronal buffer pH 6, presence of Ca(++) and amino acids, stabilization with uranyl-acetate before dehydration. The same fixation procedure applied to the DNA of vegetative phage reveals a pool of homogeneous fibrillar structure very similar to the nucleoplasm. The "versene test," which produces a coarse coagulation of these plasms, emphasizes the similar behaviour of the pool and the nucleoids. The heads of mature phage are preserved in their true polyhedral shape by the standard fixation procedure, although they may be badly distorted when fixed under different conditions. Lanthanum nitrate and uranyl-acetate are shown to increase markedly the contrast of both phage and cytoplasm. The consequences of the fibrillar structure of the genetic material are discussed in relation to the probable division process.
1,181 citations