Fernando de Castro and the discovery of the arterial chemoreceptors

Abstract

When de Castro entered the carotid body (CB) field, the organ was considered to be a small autonomic ganglion, a gland, a glomus or glomerulus, or a paraganglion. In his 1928 paper, de Castro concluded: "In sum, the Glomus caroticum is innervated by centripetal fibers, whose trophic centers are located in the sensory ganglia of the glossopharyngeal, and not by centrifugal [efferent] or secretomotor fibers as is the case for glands; these are precisely the facts which lead to suppose that the Glomus caroticum is a sensory organ." A few pages down, de Castro wrote: "The Glomus represents an organ with multiple receptors furnished with specialized receptor cells like those of other sensory organs [taste buds?]…As a plausible hypothesis we propose that the Glomus caroticum represents a sensory organ, at present the only one in its kind, dedicated to capture certain qualitative variations in the composition of blood, a function that, possibly by a reflex mechanism would have an effect on the functional activity of other organs… Therefore, the sensory fiber would not be directly stimulated by blood, but via the intermediation of the epithelial cells of the organ, which, as their structure suggests, possess a secretory function which would participate in the stimulation of the centripetal fibers." In our article we will recreate the experiments that allowed Fernando de Castro to reach this first conclusion. Also, we will scrutinize the natural endowments and the scientific knowledge that drove de Castro to make the triple hypotheses: the CB as chemoreceptor (variations in blood composition), as a secondary sensory receptor which functioning involves a chemical synapse, and as a center, origin of systemic reflexes. After a brief account of the systemic reflex effects resulting from the CB stimulation, we will complete our article with a general view of the cellular-molecular mechanisms currently thought to be involved in the functioning of this arterial chemoreceptor.

Keywords: Fernando de Castro; arterial chemoreceptorss; carotid body; ion channels; sensory physiology; transduction cascade.

FIGURE 1

Fernando de Castro (1896–1967). The picture was taken in 1967 (Courtesy of Fernando-Guillermo de Castro from the Archive Fernando de Castro).

FIGURE 2

Segment of a glomerulus of the intercarotid gland (the CB) of a young man. c, nerve with myelinated and unmyelinated fibers; a, division of myelinated fibers; b, glandular(chemoreceptor) cell; e, glandular cell with a nerve ending in mallet; g, another cell with vacuolated cytoplasm; f, fiber with varicosities; d, nerve ending forming a thick ring. Stained by the Cajal’s reduced silver nitrate method (in de Castro, 1926; courtesy of Fernando-Guillermo de Castro from the Archive Fernando de Castro).

FIGURE 3

Section from the intercarotid gland (the CB) of an adult cat 25 days after the surgical removal of the vertebral sympathetic chain. The image evidences fascicles of myelinated nerve fibers and parenchymatous cells normally innervated. The preparation was stained by the Cajal’s reduced silver nitrate method and counterstained by the carmine method of Mayer (in de Castro, 1926, , ; courtesy of Fernando-Guillermo de Castro from the Archive Fernando de Castro).

FIGURE 4

Intra carotid body arterioles (e) receiving sensory innervation from two myelinated fibers (a) which arborise to terminate preferentially in the adventitia although some endings reach the muscular layer (b). (c) Smooth muscle cells. Branches form varicosities and terminate up forming small meniscus, buttons or hammer-like endings. Note that in the lower figure the fiber and its terminals are located in the angle formed by the branching of one artery. The preparation was stained by the Cajal’s reduced silver nitrate method (in de Castro, 1926; courtesy of Fernando-Guillermo de Castro from the Archive Fernando de Castro).

FIGURE 5

Sensory ending in a tangential section in the carotid sinus of a man. (A) Thick myelinated axon that arborises in a rather beautiful pattern with different details in the terminals. (f) A branch of the main fiber. (g) Nerve terminal in racket. The preparation was stained by the Cajal’s reduced silver nitrate method (in de Castro, 1928; courtesy of Fernando-Guillermo de Castro from the Archive Fernando de Castro).

FIGURE 6

Sensoy nervous plexus in an artery of small caliber from a dog of two months. (a,b,c) Myelinated axons. (d) Varicose nerve terminal, (g,f) Terminal meniscus. The preparation was stained by the Cajal’s reduced silver nitrate method (in de Castro, 1928; courtesy of Fernando-Guillermo de Castro from the Archive Fernando de Castro).

FIGURE 7

The membrane model of acute hypoxic transduction proposes the cascade of events depicted in the figure. On lowering PO₂, an O₂^- sensor, hypothetically located in the plasma membrane, would experiment a conformational (and reversible) change, which transmitted to oxygen-regulated K⁺ channels would cause modifications in their kinetic properties, resulting in a decrease in their opening probability. The ensuing depolarization activates voltage dependent Ca²⁺ channels and entry of Ca²⁺ in the cells triggering the exocytotic release of neurotransmitters, increase in CSN action potentials and in ventilation (redrawn from González et al., 1992).