Ultrastructure of the primate carotid body: a morphometric study of the glomus cells and nerve endings in the monkey (Macaca fascicularis)

Summary The carotid body of the monkey (Macaca fascicularis) was studied at both the light and electron microscopic levels in an effort to provide a detailed quantitative characterization of this chemoreceptor organ in the primate. Structurally, the monkey carotid body was organized into lobules of from three to eight glomus cells (in section) and their ensheathing supporting cells. Interspersed among the lobules was abundant connective tissue stroma, fibroblasts and mast cells. Fenestrated capillaries, small arterioles and venules also permeated the organ. Each supporting cell partially ensheathed about three glomus cells and could be easily differentiated from glomus cells by their darker cytoplasmic staining, lack of dense-core vesicles and angular nuclear profile. Glomus cells exhibited an intense catecholamine histofluorescence and contained abundant dense-core vesicles. On the basis of dense-core vesicle size, shape and numerical density, four types of glomus cells were identified. The most common type (62% of all glomus cells) contained vesicles with an average diameter of 219 nm and a density of 8 vesicles per m² of cytoplasm. The second type possessed larger vesicles (264 nm in diameter) and accounted for about 14% of all glomus cells. A third type of glomus cell contained smaller (167 nm) and fewer (5 vesicles per m²) dense-core vesicles. The fourth type of glomus cell contained pleomorphic-shaped vesicles with a maximal diameter of 232 nm. Each of these last two types accounted for about 12% of all glomus cells. All four types of glomus cells were innervated, averaging 1.43 nerve endings per glomus cell (in sections). Nerve endings were primarily of the bouton-like variety averaging 2 m² in sectional area and containing 34.3 clear-core synaptic vesicles (average size 73.5 nm in diameter) per m² of cytoplasm. Of the 57 nerve endings examined in single sections, 16% displayed junctions typical of synaptic specializations and most of these were presynaptic to glomus cells. Glomus cell-glomus cell synapses were not observed. Based on these quantitative observations and on previous studies of carotid body cytoarchitecture in other laboratory species, it appears that the primate organ most closely resembles the cat carotid body, although several differences exist.     

The occurrence of melanosomes in the newt glomus cell

Combined light and electron microscopic observations of the carotid labyrinth of the newt, Cynops pyrrhogaster, revealed the occurrence of glomus cells with melanosomes (MG cells), a finding so far unreported in the amphibian carotid labyrinth. These melanosomes, which derived from melanophores, were electron-dense and usually oval (250-700 nm in diameter). They occurred in groups enclosed by a limiting membrane, and the diameter of clusters was approximately 1.5 microns. These clusters were surrounded by a large number of dense-cored vesicles (60-100 nm in diameter), which were predominantly located in the glomus cell cytoplasm. The density of dense-cored vesicles in MG cells was higher than that in regular glomus cells (G cells).     

Morphometric analysis of glomus cells within the recurrent laryngeal nerve of the rat

Summary An endoneurial paraganglion located in the recurrent laryngeal nerve of the rat was found in 17 of 20 nerves studied. The median size of the paraganglia was estimated to be 0.8 × 10⁶ m³. The number of type I like cells within a paraganglion ranged between 8 and 24. Altogether, 120 endoneurial dense-cored vesicle cells from 8 paraganglia were subjected to a morphometric analysis at the ultrastructure level. The mean vesicle profile diameter was estimated to be 101.3 nm and only one type of granulated cell could be distinguished. The volume density of the dense-cored vesicles was estimated to be about 6%, a value amounting to two to three times that in the carotid glomus. Moreover, the mean cell profile area of vesiculated cells of recurrent laryngeal nerve exceeds that of the cells of the carotid glomus.     

Norepinephrine-containing glomus cells in the rabbit carotid body. I. Autoradiographic and morphometric study after tritiated norepinephrine uptake

Summary Rabbit carotid bodies were investigated by autoradiography at both the light and electron microscope levels following tritiated norepinephrine administration eitherin vivo orin vitro. Two kinds of labelled structures were found: nerve fibres (absent in sympathectomized carotid bodies) and some type I glomus cells. Desipramine (a specific norepinephrine uptake inhibitor) prevented labelling. Most of the labelled cells differed from unlabelled ones by the presence of (i) large dense-cored vesicles characterized by a large halo between the membrane and an eccentric dense core; (ii) a nucleus showing a more electron dense chromatin and a more irregular shape; and (iii) relatively abundant glycogen particles. A few weakly-labelled cells were characterized by a pyknotic nucleus and very swollen dense-cored vesicles, and were presumed to be degenerating.Dense core diameters of dense-cored vesicles were distributed according to a unimodal distribution in labelled cells as in unlabelled ones but with an extension towards both large and very small diameters in labelled cells. The mean diameter was higher in labelled cells than in unlabelled ones (127 nm versus 113 nm,P < 0.01). The labelling intensity (as estimated by the number of silver grains per unit of cytoplasmic area) was maximum in cells having dense-cored vesicles whose mean diameter was between 130 and 170 nm, but decreased for cells with mean diameter of dense cores smaller than 130 nm, or larger than 170 nm.Thus, in the rabbit carotid body, some glomus cells differ from others by their ability to take up tritiated norepinephrine and by the presence of larger dense-cored vesicles. However, this distinction is not clearcut and there are many intermediates. The observations suggest a phenomenon of evolution deriving from a unique cell type and typified by both metabolic norepinephrine uptake ability, glycogen accumulation) and morphologic changes (increase in diameter of dense-cored vesicles). It seems, therefore, more appropriate to consider these results in terms of different functional states rather than different types of glomus cells.     

Ultrastructural characteristics of glomus cells in the external carotid artery during larval development and metamorphosis in bullfrogs, Rana catesbeiana.

Electron microscopic observations of the external carotid artery in the larvae of the bullfrog, Rana catesbeiana, showed that glomus cells are present in the subendothelial stroma of the septum between the expanded region of the external carotid artery and the carotid arch. There were some differences in the ultrastructure of the glomus cells at each stage of larval development. At the early stages (stages I, III, V, X), most glomus cells were isolated and free from the covering of a supporting cell. The cytoplasm of the glomus cells contained fewer dense-cored vesicles. No synaptic junctions were observed. At the middle stages (stages XV, XX, XXI), some glomus cells showed a tendency to form small clusters. Between adjacent cells in a cluster, gap junctions were often observed. The number of dense-cored vesicles increased remarkably. Intimate apposition of the glomus and smooth muscle cells (g-s connection) was also observed. Nerve terminals containing clear vesicles were observed in synaptic contact with glomus cells at this phase. At the metamorphic climax (stages XXII-XXV), in addition to g-s connections, the glomus cells made intimate apposition to the cells around the glomus cells. The afferent synapses described in other amphibians were not encountered in this study. These findings suggest that the glomus cells at the early stages of development are nonfunctional, the vascular regulation via the g-s connection starts at the middle stages, and the chemoreception starts after metamorphosis.     

Ultrastructural characteristics of glomus cells in the external carotid artery during larval development and metamorphosis in bullfrogs,Rana catesbeiana

Electron microscopic observations of the external carotid artery in the larvae of the bullfrog, Rana catesbeiana, showed that glomus cells are present in the subendothelial stroma of the septum between the expanded region of the external carotid artery and the carotid arch. There were some differences in the ultrastructure of the glomus cells at each stage of larval development. At the early stages (stages I, III, V, X), most glomus cells were isolated and free from the covering of a supporting cell. The cytoplasm of the glomus cells contained fewer dense-cored vesicles. No synaptic junctions were observed. At the middle stages (stages XV, XX, XXI), some glomus cells showed a tendency to form small clusters. Between adjacent cells in a cluster, gap junctions were often observed. The number of dense-cored vesicles increased remarkably. Intimate apposition of the glomus and smooth muscle cells (g-s connection) was also observed. Nerve terminals containing clear vesicles were observed in synaptic contact with glomus cells at this phase. At the metamorphic climax (stages XXII–XXV), in addition to g-s connections, the glomus cells made intimate apposition to the cells around the glomus cells. The afferent synapses described in other amphibians were not encountered in this study. These findings suggest that the glomus cells at the early stages of development are nonfunctional, the vascular regulation via the g-s connection starts at the middle stages, and the chemoreception starts after metamorphosis. © 1992 Wiley-Liss, Inc.     

Intimate apposition of the glomus and smooth muscle cells (g-s connection) in the carotid labyrinth of juvenile bullfrogs

Summary Intimate apposition of the glomus and smooth muscle cells (g-s connection) was found in almost all glomus cells of the carotid labyrinths in juvenile bullfrogs, Rana catesbeiana. There were three types of g-s connection: between thin processes (0.1–0.2 m in width) without dense-cored vesicles of glomus cells and smooth muscle cells; between thick processes (1.0–1.5 m in width) with dense-cored vesicles of glomus cells and smooth muscle cells; and between the tonguelike projections of smooth muscle cells and the flat surface of the glomus cell. In some cases, a single glomus cell made g-s connections with several smooth muscle cells. Exocytosis often occurs at the g-s connection. Afferent and efferent synapses were found on the glomus cells with g-s connections. Reciprocal synapses were also observed. On the basis of these findings, the second and third types of g-s connection are presumed to participate in vascular regulation.     

Norepinephrine-containing glomus cells in the rabbit carotid body. II. Immunocytochemical evidence of dopamine-beta-hydroxylase and norepinephrine.

Summary The presence of noradrenergic glomus cells in the rabbit carotid body was investigated at the light and electron microscope levels, using dopamine-ß-hydroxylase and norepinephrine immunocytochemistry as well as the chromaffin reaction.Frozen and semi-thin plastic sections showed some dopamine-ß-hydroxylase immunoreactive glomus cells either isolated in the connective tissue or, more frequently, mixed with unreactive cells. At the ultrastructural level, immunopositive cells differed from immunonegative ones by the larger size of most of their dense-cored vesicles. Similar observations were made after using anti-norepinephrine antibodies. Immunoreactive cells to anti-dopamine-ß-hydroxylase and anti-norepinephrine antibodies were relatively few although their number varied from carotid body to carotid body. The immunolabelling intensity was very variable from cell to cell. Consecutive frozen sections processed for norepinephrine- and dopamine-immunocytochemistry showed many cell clusters containing both norepinephrine and dopamine-immunoreactive glomus cells.Some chromaffin glomus cells were clearly identifiable by the very strong electron opacity of their dense-cored vesicles; most of these vesicles were characterized by their large size, as the dense-cored vesicles observed in dopamine-ß-hydroxylase- and norepinephrine-immunopositive cells.These results demonstrated that dopamine-ß-hydroxylase and norepinephrine-immunopositive, as well as chromaffin cells, were identical to the cells which take up exogeneous norepinephrine, described in part I of this study. However, many intermediate levels were found between norepinephrine-immunonegative and strongly norepinephrine-immunopositive glomus cells, suggesting that the distinction between these two kinds of cells is not clearcut.     

Postnatal development of carotid body glomus cell O2 sensitivity

In mammals, the main sensors of arterial oxygen level are the carotid chemoreceptors, which exhibit low sensitivity to hypoxia at birth and become more sensitive over the first few days or weeks of life. This postnatal increase in hypoxia sensitivity of the arterial chemoreceptors, termed "resetting", remains poorly understood. In the carotid body, hypoxia is transduced by glomus cells, which are secretory sensory neurons that respond to hypoxia at higher P(O2) levels than non-chemoreceptor cell types. Maturation or resetting of carotid body O2 sensitivity potentially involves numerous aspects of the O2 transduction cascade at the glomus cell level, including glomus cell neurotransmitter secretion, neuromodulator function, neurotransmitter receptor expression, glomus cell depolarization in response to hypoxia, [Ca2+]i responses to hypoxia, K+ and Ca2+ channel O2 sensitivity and K+ channel expression. However, although progress has been made in the understanding of carotid body development, the precise mechanisms underlying postnatal maturation of these numerous aspects of chemotransduction remain obscure.     

Endocytosis of cationized ferritin to vesicles in the Golgi region of the glomus cells dissociated from the adult rat carotid body

Glomus cells were dissociated from the carotid bodies of adult rats by enzymatic digestion with collagenase. The cells were then incubated at 37 degrees C for 30 minutes to 3 hours in the continuous presence of cationized ferritin (CF) as a membrane marker and extracellular tracer to study the intracellular route of endocytosis in this cell type. After 30 minutes of incubation with CF, occasional solitary CF-containing vesicles were observed at the cell periphery and also in the Golgi region. After 2-3 hours of incubation with CF, cell viability was still preserved and CF-labeled vesicles were abundant in the Golgi region. CF particles were also seen in some vesicles having a dense core. The core of these labeled vesicles appeared to be less electron-dense than that of typical secretory granules. It is suggested that the Golgi apparatus is involved in membrane recycling in glomus cells and that the membrane is then possibly further transported to an immature type of storage vesicle for reusage.     

The spatial relationship between type I glomus cells and arteriolar myocytes in the mouse carotid body

The structural relationship between type I glomus cells and the vascular smooth muscle was investigated by electron microscopy in the mouse carotid body. A close apposition (<0.1 μm) between the glomus parenchyma and the neighbouring arterioles was regularly present. Profiles of type I glomus cells were found to be exposed to the vascular smooth muscle without any supporting cell investment. In circumscribed areas of these profiles, type I glomus cells and the vascular smooth muscle cells made contact by fusion of their basal laminae. These glomus-cell-myocyte junctions structurally resemble vascular neuromuscular junctions of sympathetic nerve terminals. In addition to the occurrence of such glomus cell-myocyte contacts, myoendothelial junctions also appeared frequently. On the basis of these observations, it is suggested that type I glomus cells play a role in the regulation of the vascular tone in the carotid body and that a physiological interaction between the endothelial cells, the vascular smooth muscle cells and the type I glomus cells exists.     

Changes in oxygen sensitivity of TASK in carotid body glomus cells during early postnatal development

A post-natal increase in carotid body (CB) hypoxia responsiveness occurs at the level of carotid sinus nerve activity, intracellular calcium, cell membrane depolarization and hypoxic inhibition of O(2)-sensitive background K(+) conductance. TASK-1, TASK-1/3 and TASK-3 are functionally expressed in CB glomus cells, with TASK-1/3 providing the major part of the O(2)-sensitive TASK-like background K(+) conductance. Here we report the effects of graded hypoxia on TASK-like channel activity in CB glomus cells from rats aged 0 to 1, 6 to 7 and 16 to 18 days; the time frame of postnatal CB functional maturation. TASK was active in nearly all cell-attached patches and TASK activity during normoxia did not differ across ages. Hypoxia produced a progressive decrease in channel opening frequency with graded decreases in O(2) level and also produced glomus cell depolarization, as assessed by the shift in reversal potential of TASK single channel current. Hypoxic inhibition of TASK activity was least at P0-P1 and increased with age mainly between 6-7 and 16-18 days. The O(2)-sensitive TASK activity was significantly greater in glomus cells from P16 to P18 when compared to cells from P0 to P1 day old rats. These results support the hypothesis that postnatal carotid body functional maturation is due, at least in part, to changes in the sensitivity of TASK to the hypoxic signals generated in glomus cells.     

Patch clamp study of mouse glomus cells using a whole carotid body

Some electrophysiological characteristics of mouse glomus cells (DBA/2J strain) were investigated using an undissociated carotid body. The carotid body with major carotid arteries was placed in a recording chamber, and glomus cells were visualized with a water immersion lens combined with an infrared differential interference video camera. Patch clamp experiments revealed that voltage-gated outward current, but not inward current, was easily observed in glomus cells. Pharmacological experiments and the kinetics of the current suggest that outward current is via delayed rectifier, A type, and large conductance calcium-activated K channels. Furthermore, K current was reversibly attenuated by mild hypoxia. The results suggest electrophysiological similarities of glomus cells among the cat, the rat, and the DBA/2J mouse. The method appears useful for physiological experiments.     

Histochemical evidence of adenosine triphosphatase activity in glomus tumor--report of a case

A case of glomus tumor was studied by light and electron microscopic enzyme histochemistry. Histologically, this case was classified as glomangioma or vascular form of glomus tumor. The tumor cells had ultrastructural characteristics of smooth muscle cells such as large amount of thin filaments with dense bodies, basal lamina and numerous pinocytotic vesicles. Among the 3 membrane associated enzymes, namely alkaline phosphatase, adenosine triphosphatase (ATPase) and 5'nucleotidase, only ATPase was detectable in the cell membrane and pinocytotic vesicles. It is suggested that the ATPase activity of the tumor cells shows additional evidence of smooth muscle character of glomus tumor.     

Augmentation of L-type calcium current by hypoxia in rabbit carotid body glomus cells: evidence for a PKC-sensitive pathway

Previous studies have suggested that voltage-gated Ca(2+) influx in glomus cells plays a critical role in sensory transduction at the carotid body chemoreceptors. The purpose of the present study was to determine the effects of hypoxia on the Ca(2+) current in glomus cells and to elucidate the underlying mechanism(s). Experiments were performed on freshly dissociated glomus cells from rabbit carotid bodies. Ca(2+) current was monitored using the whole cell configuration of the patch-clamp technique, with Ba(2+) as the charge carrier. Hypoxia (pO(2) = 40 mmHg) augmented the Ca(2+) current by 24 +/- 3% (n = 42, at 0 mV) in a voltage-independent manner. This effect was seen in a CO(2)/HCO(3)(-)-, but not in a HEPES-buffered extracellular solution at pH 7.4 (n = 6). When the pH of a HEPES-buffered extracellular solution was lowered from 7.4 to 7. 0, hypoxia augmented the Ca(2+) current by 20 +/- 5% (n = 4, at 0 mV). Nisoldipine, an L-type Ca(2+) channel blocker (2 microM, n = 6), prevented, whereas, omega-conotoxin MVIIC (2 microM, n = 6), an inhibitor of N and P/Q type Ca(2+) channels, did not prevent augmentation of the Ca(2+) current by hypoxia, implying that low oxygen affects L-type Ca(2+) channels in glomus cells. Protein kinase C (PKC) inhibitors, staurosporine (100 nM, n = 6) and bisindolylmaleimide (2 microM, n = 8, at 0 mV), prevented, whereas, a protein kinase A inhibitor (4 nM PKAi, n = 10) did not prevent the hypoxia-induced increase of the Ca(2+) current. Phorbol 12-myristate 13-acetate (PMA, 100 nM), a PKC activator, augmented the Ca(2+) current by 20 +/- 3% (n = 8, at 0 mV). In glomus cells treated with PMA overnight (100 nM), hypoxia did not augment the Ca(2+) current (-3 + 4%, n = 5, at 0 mV). Immunocytochemical analysis revealed PKCdelta-like immunoreactivity in the cytosol of the glomus cells. Following hypoxia (6% O(2) for 5 min), PKCdelta-like immunoreactivity translocated to the plasma membrane in 87 +/- 3% of the cells, indicating PKC activation. These results demonstrate that hypoxia augments Ca(2+) current through L-type Ca(2+) channels via a PKC-sensitive mechanism.     

Fine structure of the carotid body of the midterm human fetus

Summary The human fetal carotid body was studied using both histochemical and electron microscopic methods. The glomus cells of a mid term fetal carotid body evidently contain catecholamines. This was demonstrated both by formaldehyder-induced fluorescence of the cells and by the presence of typical dense-cored vesicles (diameter 1430–3200 Å) in the cytoplasm of the chief cells. The glomus cells were densely innervated and the synapses found on their surface were probably cholinergic in type, containing agranular synaptic vesicles measuring 400–700 Å in diameter with a few dense-cored vesicles measuring 900 to 1300 Å. Synapses were not found in any other cell type within the glomus caroticum. The prominent feature of the glomus cell cytoplasm was the presence of the dense-cored vesicles. The density of the vesicular core varied only slightly from cell to cell. There were no perceptible differences in vesicular size between the different cells. The glomus cells were mostly surrounded by the processes of the sustentacular cells, which usually also surrounded the capillary walls. No glomus cells were ever found in direct contact with the capillary wall. The capillaries were wide and very numerous over the restricted area of the organ. They formed sinusoidal loops, probably anastomosing with each other. Finally, the features of the fine structure are discussed, correlating the present findings with our knowledge about the adult functional carotic body.     

HERG-Like potassium current regulates the resting membrane potential in glomus cells of the rabbit carotid body

Direct evidence for a specific K(+) channel underlying the resting membrane potential in glomus cells of the carotid body has been absent. The product of the human ether-a-go-go-related gene (HERG) produces inward rectifier currents that are known to contribute to the resting membrane potential in other neuronal cells. The goal of the present study was to determine whether carotid body glomus cells express HERG-like K(+) current, and if so, to determine whether a HERG-like current regulates the resting membrane potential. Freshly dissociated rabbit glomus cells under whole cell voltage clamp exhibited slowly decaying outward currents that activated 20-30 mV positive to the resting membrane potential. Raising extracellular K(+) revealed a slowly deactivating inward tail current indicative of HERG-like K(+) current. HERG-like currents were not found in cells resembling type II cells. The HERG-like current was blocked by dofetilide (DOF) in a concentration-dependent manner (IC(50) = 13 +/- 4 nM, mean +/- SE) and high concentrations of Ba(2+) (1 and 10 mM). The biophysical and pharmacological characteristics of this inward tail current suggest that it is conducted by a HERG-like channel. The steady-state activation properties of the HERG-like current (V(h) = -44 +/- 2 mV) suggest that it is active at the resting membrane potential in glomus cells. In whole cell, current-clamped glomus cells (average resting membrane potential, - 48 +/- 4 mV), DOF, but not tetraethylammonium, caused a significant (13 mV) depolarizing shift in the resting membrane potential. Using fluorescence imaging, DOF increased [Ca(2+)](i) in isolated glomus cells. In an in-vitro carotid body preparation, DOF increased basal sensory discharge in the carotid sinus nerve in a concentration-dependent manner. These results demonstrate that glomus cells express a HERG-like current that is active at, and responsible for controlling the resting membrane potential.     

Carotid body thin slices: responses of glomus cells to hypoxia and K(+)-channel blockers

We describe the rat carotid body thin slice preparation, which allows to perform patch-clamp recording of membrane ionic currents and to monitor catecholamine secretion by amperometry in single glomus cells under direct visual control. We observed several electrophysiologically distinct cell classes within the same glomerulus. A voltage- and Ca(2+)-dependent component of the whole cell K(+) current was reversibly inhibited by low P(O(2)) (20 mmHg). Exposure of the cells to hypoxia elicited the appearance of spike-like exocytotic events. This response to hypoxia was reversible and required extracellular Ca(2+) influx. Addition of tetraethylammonium (TEA, 2-5 mM) to the extracellular solution induced in most (>95%) cells tested a secretory response similar to that elicited by low P(O(2)). Cells non-responsive to hypoxia but activated by exposure to high external K(+) were also stimulated by TEA. A secretory response similar to that of hypoxia or TEA was also observed after treatment of the cells with iberiotoxin to block selectively maxi-K(+) channels. Our data further support the view that membrane ion channels are critically involved in sensory transduction in the carotid body. We demonstrate that in intact glomus cells inhibition of voltage-dependent K(+) channels can contribute to initiate the secretory response to low P(O(2)).     

Type I cells of carotid body from rats treated with 5-OH-Dopa and L-Dopa: an electron microscopical study

Summary The ultrastructure of the Type I cells in rat carotid bodies was studied after treatment with 5-OH-Dopa and L-Dopa. Type I cells from the L-Dopa treated rats were also analysed by morphometric methods.After 5-OH-Dopa treatment, the majority of dense-cored vesicles of the Type I cells were almost completely filled withvery electron-dense material. The vesicles were mainly distributed close to the plasma membrane.After L-Dopa treatment, the ultrastructure of the Type I cells resembled that after 5-OH-Dopa treatment, except that the increase in electron density of the vesicle content was less pronounced. The morphometric analysis revealed, as previously described for normal carotid bodies, two subclasses of Type I cells, small vesicle cells (SVC) and large vesicle cells (LVC). Compared to those of normal rats, the mean profile diameter of the vesicles in theL-Dopa treated rat carotid bodies were enlarged (for SVC from 47 to 55 nm and for LVC from 63 to 76–78 nm). Furthermore, the volume density of vesicles in both SVC and LVC was increased. The mean volume of the SVC was markedly increased after L-Dopa treatment for 60 h.These observations indicate that the Type I cells possess mechanisms for uptake of amine precursors and synthesis of monoamines. Though the vesicle may be involved in an endocrine-like function, they may also be related to the chemoreceptor function of the carotid body.     

Inhibition of rat carotid body glomus cells TASK-like channels by acute hypoxia is enhanced by chronic intermittent hypoxia

Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) chemosensory responses to acute hypoxia. In spite of that, the primary molecular target of CIH in the CB remains unknown. A key step of the hypoxic response in the CB is the chemoreceptor cell depolarization elicited by the inhibition of K⁺ channels. Thus, we tested the hypothesis that CIH potentiates the hypoxic-induced depolarization of rat CB chemoreceptor cells by enhancing the inhibition of a background K⁺ TASK-like channel. Membrane potential, single channel and macroscopic currents were recorded in the presence of TEA and 4-aminopyridine in CB chemoreceptor cells isolated from adult rats exposed to CIH. The CIH treatment did not modify the resting membrane properties but the hypoxic-evoked depolarization increased by 2-fold. In addition, the hypoxic inhibition of the TASK-like channel current was larger and faster in glomus cells from CIH-treated animals. This novel effect of CIH may contribute to explain the enhancing effect of CIH on CB oxygen chemoreception.