Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Chemoreceptor”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources
PubMed1988

Chemoreceptor control of heart rate and behaviour during diving in the tufted duck (Aythya fuligula).

1. The role of chemoreceptors in the control of heart rate and behaviour during diving activity in the tufted duck was investigated in two ways. In a closed-loop experiment, ducks were exposed to ambient gas mixtures of varied composition during diving activity in an indoor tank. Characteristics of diving behaviour, heart rate and deep body temperature were monitored under hypoxic, hyperoxic and hypercapnic conditions and compared with those in air. Secondly, in an open-loop experiment the role of the carotid body (CB) chemoreceptors in the control of the responses to altered inspired gas composition and in the cardiac responses to extended and enclosed dives (Stephenson, Butler & Woakes, 1986) was investigated by chronic bilateral denervation of these receptors. 2. Heart rate during submersion was unaffected by inspired gas composition in control (data from intact and sham-operated ducks combined) and CB-denervated ducks, though diving behaviour was significantly modified in both groups of animals in response to altered inspired gas composition. Hypoxia and hypercapnia resulted in an increase in the proportion of total diving time spent breathing at the surface. The main effect of hypoxia (9-10% O2) was to reduce dive duration in control ducks and this effect was almost completely abolished after CB denervation. Hypercapnia (5-6% CO2) reduced dive duration less markedly than hypoxia but it greatly increased the duration of the inter-dive interval, effects which were not significantly influenced by CB denervation. Hyperoxia (40-45% O2) had very little effect on either behaviour or heart rate during diving, although deep body temperature was significantly elevated in this gas mixture during diving activity. There was also a less marked, but nevertheless significant, apparent hyperthermia during diving activity in air on an indoor tank but not on an outdoor pond. Conversely, there was a significant apparent hypothermia during diving activity under hypoxic conditions. 3. The CB chemoreceptors were shown to play a role in cardiac control during diving under certain circumstances. The duration of pre-dive tachycardia was significantly increased in hypoxia and this increase was abolished after CB denervation. The rate of development of bradycardia during extended and enclosed dives was slowed following CB denervation, though the initiation of the responses in extended and enclosed dives and the eventual attainment of sub-resting heart rates in enclosed dives were not prevented, indicating that other, as yet unidentified, sensory inputs are involved in cardiac control under these conditions.

Animals↗
PubMed1988

Effects of potassium, oxygen and carbon dioxide on the steady-state discharge of cat carotid body chemoreceptors.

1. We have studied the effects of intravenous infusions of 0.1 mmol/min KCl (raising arterial potassium from ca. 3.2 to 6.0 mM) on the steady-state responses of carotid body chemoreceptors to end-tidal PCO2 and PO2 in the pentobarbitone-anaesthetized cat. 2. The excitatory effect of these KCl infusions was enhanced by hypoxia and reduced or abolished by hyperoxia. 3. Hypercapnia did not enhance, and usually reduced, excitation by KCl. 4. When similar control discharge frequencies were established by hypoxia or by hypercapnia, a KCl infusion excited the hypoxic discharge by about twice as much as it did the hypercapnic discharge. 5. These observations are not inconsistent with the idea that the mechanism underlying hypoxic excitation of arterial chemoreceptors is one that controls extracellular potassium concentration near the afferent nerve ending. 6. Insofar as potassium-induced excitation of chemoreceptor discharge is abruptly reduced by hyperoxia it behaves like Asmussen and Nielsen's postulated 'anaerobic work substance' and it may therefore contribute to the increased importance of the arterial chemoreflex reported in exercise.

Action Potentials↗
PubMed1988

Localization by kainic acid lesions of neurones transmitting the carotid chemoreceptor stimulus for respiration in rat.

1. An attempt has been made to test the hypothesis that in the nucleus of the tractus solitarius (NTS) in the rat, the most caudal region of synaptic terminals of the carotid sinus nerve, just caudal to the obex, represents mainly the site of synapse of chemoreceptor fibres from the carotid body. 2. Under halothane anaesthesia, the neurotoxin kainic acid was used to lesion this region and a second region, immediately rostral to obex, where terminals are thought to arise mainly from baroreceptor fibres of the carotid sinus nerve. 3. Measurements based on the distribution of fluorescent dye co-injected with the kainic acid showed that the two groups of 100 nl microinjections were centered 0.82 mm apart and that the injectate spread through mean distances of 0.57 mm (caudal microinjections) and 0.52 mm (rostral microinjections). Nissl staining was used to determine cellular degeneration. The caudal lesions mostly involved ventrolateral and commissural subnuclei of NTS and the rostral lesions involved lateral and dorsolateral subnuclei. 4. Ventilatory sensitivity to hypoxia was tested under light halothane anaesthesia, 1 day after lesioning. To enhance the responses, the contralateral carotid sinus nerve was sectioned prior to experiments. Caudal lesions reduced the ventilatory response to inspired oxygen (20.9-9.6% O2) by a mean of 67% and rostral lesions by 18% of the effect produced by carotid sinus nerve section on that side. Subsequent section of the carotid sinus nerve on the side of the NTS lesion confirmed that caudal lesions produced effects comparable to those of carotid body denervation; rostral lesions did not. 5. These results strongly support the hypothesis that chemoreceptor and baroreceptor afferent fibres in the carotid sinus nerve synapse at substantially separable sites in the nucleus of the tractus solitarius. The identification of the site in NTS caudal to the obex as the principal site of carotid chemoreceptor synapses places them close to but not upon respiratory premotor neurones of the same nucleus.

Animals↗
PubMed1990

Carotid body chemoreceptor response to prolonged hypoxia in the rabbit: effects of domperidone and propranolol.

1. The discharge of single afferent chemoreceptor fibres was recorded from the cut sinus nerve over periods of 60 or 90 min of constant, isocapnic hypoxia (arterial O2 pressure, Pa,O2, 3.13-5.25 kPa), in twenty anaesthetized rabbits, after dividing the sympathetic supply to the carotid body. 2. Under control conditions, discharge after 60 min of hypoxia adapted to a mean (S.E.M.) of 71.95 (2.75)% of that attained at 5 min of hypoxia in twenty-three hypoxic experiments. This adaptation was more pronounced when Pa,O2 was lower than 4 kPa (30 Torr). 3. Domperidone (1 mg kg-1 bolus + 1 mg kg-1 h-1 infusion I.V.), increased normoxic afferent discharge by a mean of 142%. In ten experiments, discharge after 60 min of hypoxia adapted to a mean (S.E.M.) of 56.22 (+/- 3.40)% of that attained at 5 min of hypoxia which was significantly different from control hypoxic runs (P = 0.006). 4. In seven experiments propranolol (1 mg kg-1 bolus + 1 mg kg-1 h-1 infusion I.V.) did not affect the normoxic discharge. The mean adaptation of discharge after 60 min of hypoxia was to 77.43 (3.97)% of discharge attained at 5 min of hypoxia, which was not significantly different from control hypoxic runs (P = 0.34). 5. Under control conditions plasma [K+] increased steadily during 60 min of hypoxia, in fourteen experiments, from a mean of 2.76 (0.14) to 2.85 (0.12) mmol l-1 but this was not significant (P = 0.21). Domperidone (n = 6) did not affect plasma [K+] at any time, but after propranolol (n = 6) it increased by a mean (S.E.M.) of 0.39 (0.09) mmol l-1 (P = 0.01) in normoxia and by a further 0.62 (0.28) mmol l-1 (P = 0.08) at 60 min of hypoxia. 6. The results suggest that the adaptation of chemoreceptor discharge to hypoxia in the rabbit is not mediated by changes in plasma [K+]; in addition, endogenous dopamine, but not noradrenaline, contributes to the maintenance of chemoreceptor discharge in prolonged hypoxia.

Action Potentials↗
PubMed2004

Characterization of the Kv channels of mouse carotid body chemoreceptor cells and their role in oxygen sensing.

As there are wide interspecies variations in the molecular nature of the O(2)-sensitive Kv channels in arterial chemoreceptors, we have characterized the expression of these channels and their hypoxic sensitivity in the mouse carotid body (CB). CB chemoreceptor cells were obtained from a transgenic mouse expressing green fluorescent protein (GFP) under the control of tyrosine hydroxylase (TH) promoter. Immunocytochemical identification of TH in CB cell cultures reveals a good match with GFP-positive cells. Furthermore, these cells show an increase in [Ca(2+)](i) in response to low P(O(2)), demonstrating their ability to engender a physiological response. Whole-cell experiments demonstrated slow-inactivating K(+) currents with activation threshold around -30 mV and a bi-exponential kinetic of deactivation (tau of 6.24 +/- 0.52 and 32.85 +/- 4.14 ms). TEA sensitivity of the currents identified also two different components (IC(50) of 17.8 +/- 2.8 and 940.0 +/- 14.7 microm). Current amplitude decreased reversibly in response to hypoxia, which selectively affected the fast deactivating component. Hypoxic inhibition was also abolished in the presence of low (10-50 microm) concentrations of TEA, suggesting that O(2) interacts with the component of the current most sensitive to TEA. The kinetic and pharmacological profile of the currents suggested the presence of Kv2 and Kv3 channels as their molecular correlates, and we have identified several members of these two subfamilies by single-cell PCR and immunocytochemistry. This report represents the first functional and molecular characterization of Kv channels in mouse CB chemoreceptor cells, and strongly suggests that O(2)-sensitive Kv channels in this preparation belong to the Kv3 subfamily.

Animals↗
PubMed2004

Neuroepithelial oxygen chemoreceptors of the zebrafish gill.

In aquatic vertebrates, hypoxia induces physiological changes that arise principally from O(2) chemoreceptors of the gill. Neuroepithelial cells (NECs) of the zebrafish gill are morphologically similar to mammalian O(2) chemoreceptors (e.g. carotid body), suggesting that they may play a role in initiating the hypoxia response in fish. We describe morphological changes of zebrafish gill NECs following in vivo exposure to chronic hypoxia, and characterize the cellular mechanisms of O(2) sensing in isolated NECs using patch-clamp electrophysiology. Confocal immunofluorescence studies indicated that chronic hypoxia (P(O(2)) = 35 mmHg, 60 days) induced hypertrophy, proliferation and process extension in NECs immunoreactive for serotonin or synaptic vesicle protein (SV2). Under voltage clamp, NECs responded to hypoxia (P(O(2)) = 25-140 mmHg) with a dose-dependent decrease in K(+) current. The current-voltage relationship of the O(2)-sensitive current (I(KO(2))) reversed near E(K) and displayed open rectification. Pharmacological characterization indicated that I(KO(2)) was resistant to 20 mM tetraethylammonium (TEA) and 5 mM 4-aminopyridine (4-AP), but was sensitive to 1 mm quinidine. In current-clamp recordings, hypoxia produced membrane depolarization associated with a conductance decrease; this depolarization was blocked by quinidine, but was insensitive to TEA and 4-AP. These biophysical and pharmacological characteristics suggest that hypoxia sensing in zebrafish gill NECs is mediated by inhibition of a background K(+) conductance, which generates a receptor potential necessary for neurosecretion and activation of sensory pathways in the gill. This appears to be a fundamental mechanism of O(2) sensing that arose early in vertebrate evolution, and was adopted later in mammalian O(2) chemoreceptors.

Animals↗
PubMed2005

Interaction of chemoreceptor and baroreceptor reflexes by hypoxia and hypercapnia - a mechanism for promoting hypertension in obstructive sleep apnoea.

Asphyxia, which occurs during obstructive sleep apnoeic events, alters the baroreceptor reflex and this may lead to hypertension. We have recently reported that breathing an asphyxic gas resets the baroreceptor-vascular resistance reflex towards higher pressures. The present study was designed to determine whether this effect was caused by the reduced oxygen tension, which affects mainly peripheral chemoreceptors, or by the increased carbon dioxide, which acts mainly on central chemoreceptors. We studied 11 healthy volunteer subjects aged between 20 and 55 years old (6 male). The stimulus to the carotid baroreceptors was changed using graded pressures of -40 to +60 mmHg applied to a neck chamber. Responses of vascular resistance were assessed in the forearm from changes in blood pressure (Finapres) divided by brachial blood flow velocity (Doppler) and cardiac responses from the changes in RR interval and heart rate. Stimulus-response curves were defined during (i) air breathing, (ii) hypoxia (12% O(2) in N(2)), and (iii) hypercapnia (5% CO(2) in 95% O(2)). Responses during air breathing were assessed both prior to and after either hypoxia or hypercapnia. We applied a sigmoid function or third order polynomial to the curves and determined the maximal differential (equivalent to peak sensitivity) and the corresponding carotid sinus pressure (equivalent to 'set point'). Hypoxia resulted in an increase in heart rate but no significant change in mean blood pressure or vascular resistance. However, there was an increase in vascular resistance in the post-stimulus period. Hypoxia had no significant effect on baroreflex sensitivity or 'set point' for the control of RR interval, heart rate or mean arterial pressure. Peak sensitivity of the vascular resistance response to baroreceptor stimulation was significantly reduced from -2.5 +/- 0.4 units to -1.4 +/- 0.1 units (P < 0.05) and this was restored in the post-stimulus period to -2.6 +/- 0.5 units. There was no effect on 'set point'. Hypercapnia, on the other hand, resulted in a decrease in heart rate, which remained reduced in the post-stimulus period and significantly increased mean blood pressure. Baseline vascular resistance was significantly increased and then further increased in the post-control period. Like hypoxia, hypercapnia had no effect on baroreflex control of RR interval, heart rate or mean arterial pressure. There was, also no significant change in the sensitivity of the vascular resistance responses, however, 'set point' was significantly increased from 74.7 +/- 4 to 87.0 +/- 2 mmHg (P < 0.02). This was not completely restored to pre-stimulus control levels in the post-stimulus control period (82.2 +/- 3 mmHg). These results suggest that the hypoxic component of asphyxia reduces baroreceptor-vascular resistance reflex sensitivity, whilst the hypercapnic component is responsible for increasing blood pressure and reflex 'set point'. Hypercapnia appears to have a lasting effect after the removal of the stimulus. Thus the effect of both peripheral and central chemoreceptors on baroreflex function may contribute to promoting hypertension in patients with obstructive sleep apnoea.

Adult↗
PubMed2006

Central chemoreceptors and sympathetic vasomotor outflow.

The present study explores how elevations in brain P(CO(2)) increase the sympathetic nerve discharge (SND). SND, phrenic nerve discharge (PND) and putative sympathoexcitatory vasomotor neurons of the rostral ventrolateral medulla (RVLM) were recorded in anaesthetized sino-aortic denervated and vagotomized rats. Hypercapnia (end-expiratory CO(2) from 5% to 10%) increased SND (97 +/- 6%) and the activity of RVLM neurons (67 +/- 4%). Injection of kynurenic acid (Kyn, ionotropic glutamate receptor antagonist) into RVLM or the retrotrapezoid nucleus (RTN) eliminated or reduced PND, respectively, but did not change the effect of CO(2) on SND. Bilateral injection of Kyn or muscimol into the rostral ventral respiratory group (rVRG-pre-Bötzinger region, also called CVLM) eliminated PND while increasing the stimulatory effect of CO(2) on SND. Muscimol injection into commissural part of the solitary tract nucleus (commNTS) had no effect on PND or SND activation by CO(2). As expected, injection of Kyn into RVLM or muscimol into commNTS virtually blocked the effect of carotid body stimulation on SND in rats with intact carotid sinus nerves. In conclusion, CO(2) increases SND by activating RVLM sympathoexcitatory neurons. The relevant central chemoreceptors are probably located within or close to RVLM and not in the NTS or in the rVRG-pre-Bötzinger/CVLM region. RVLM sympathoexcitatory neurons may be intrinsically pH-sensitive and/or receive excitatory synaptic inputs from RTN chemoreceptors. Activation of the central respiratory network reduces the overall sympathetic response to CO(2), presumably by activating barosensitive CVLM neurons and inhibiting RTN chemoreceptors.

Action Potentials↗
PubMed1998

Effects of almitrine bismesylate on the ionic currents of chemoreceptor cells from the carotid body.

Almitrine is a drug used in the treatment of hypoxemic chronic lung diseases such as bronchitis and emphysema because it is a potent stimulant of the carotid bodies in human and different animal species that produces a long-lasting enhancement of alveolar ventilation, ameliorating arterial blood gases. However, the mechanism of action of almitrine remains unknown. We investigated the effect of almitrine on ionic currents of chemoreceptor cells isolated from the carotid body of rat and rabbits by using the whole-cell and inside-out configurations of the patch-clamp technique. Almitrine at concentrations up to 10 microM did not affect whole-cell voltage-dependent K+, Ca2+, or Na+ currents in rat or rabbit cells. However, this concentration of almitrine significantly inhibited the Ca2+-dependent component of K+ currents in rat chemoreceptor cells. This effect of almitrine on the Ca2+-dependent component of K+ currents was investigated further at the single-channel level in excised patches in the inside-out configuration. In this preparation, almitrine inhibited the activity of a high-conductance (152 +/- 13 pS), Ca2+-dependent K+ channel by decreasing its open probability. The IC50 value of the effect was 0. 22 microM. The inhibitory effect of almitrine on Ca2+-dependent K+ channels also was observed in GH3 cells. We conclude that almitrine inhibits selectively the Ca2+-dependent K+ channel and that in rat chemoreceptor cells, this inhibition could represent an important mechanism of action underlying the therapeutic actions of the drug.

Almitrine↗
PubMed2006

Mutationally altered signal output in the Nart (NarX-Tar) hybrid chemoreceptor.

Signal-transducing proteins that span the cytoplasmic membrane transmit information about the environment to the interior of the cell. In bacteria, these signal transducers include sensor kinases, which typically control gene expression via response regulators, and methyl-accepting chemoreceptor proteins, which control flagellar rotation via the CheA kinase and CheY response regulator. We previously reported that a chimeric protein (Nart) that joins the ligand-binding, transmembrane, and linker regions of the NarX sensor kinase to the signaling and adaptation domains of the Tar chemoreceptor elicits a repellent response to nitrate and nitrite. As with NarX, nitrate evokes a stronger response than nitrite. Here we show that mutations targeting a highly conserved sequence (the P box) in the periplasmic domain alter chemoreception by Nart and signaling by NarX similarly. In particular, the G51R substitution converts Nart from a repellent receptor into an attractant receptor for nitrate. Our results underscore the conclusion that the fundamental mechanism of transmembrane signaling is conserved between homodimeric sensor kinases and chemoreceptors. They also highlight the plasticity of the coupling between ligand binding and signal output in these systems.

Bacterial Proteins↗
PubMed1990

Role of threonine residue 154 in ligand recognition of the tar chemoreceptor in Escherichia coli.

The Tar chemoreceptor of Escherichia coli mediates attractant responses to aspartate, maltose, and phenol, repellent responses to Ni2+ and Co2+, and thermoresponses. To understand the role of threonine residue 154, which is located in the ligand-binding domain of Tar, we replaced the residue with serine, isoleucine, and proline by site-directed mutagenesis. The replacements caused reductions in aspartate sensing but had only a small effect on maltose sensing and almost no effect on phenol sensing, repellent sensing, and thermosensing. These results indicate that Thr-154 of Tar is rather specifically involved in aspartate sensing. The reductions in the response threshold for aspartate by the replacements with serine, isoleucine, and proline were less than 1, about 2, and more than 5 orders of magnitude, respectively. When the corresponding threonine residue in the Tsr chemoreceptor was replaced with the same amino acids, roughly similar reductions in the response threshold for serine resulted. Thus, these threonine residues seem to have a common role in detecting the aspartate and serine attractant families. A mechanism by which these chemoreceptors detect the amino acid attractants is discussed.

Aspartic Acid↗
PubMed1998

Chemotactic adaptation is altered by changes in the carboxy-terminal sequence conserved among the major methyl-accepting chemoreceptors.

In Escherichia coli and Salmonella typhimurium, methylation and demethylation of receptors are responsible for chemotactic adaptation and are catalyzed by the methyltransferase CheR and the methylesterase CheB, respectively. Among the chemoreceptors of these species, Tsr, Tar, and Tcp have a well-conserved carboxy-terminal motif (NWET/SF) that is absent in Trg and Tap. When they are expressed as sole chemoreceptors, Tsr, Tar, and Tcp support good adaptation, but Trg and Tap are poorly methylated and supported only weak adaptation. It was recently discovered that CheR binds to the NWETF sequence of Tsr in vitro. To examine the physiological significance of this binding, we characterized mutant receptors in which this pentapeptide sequence was altered. C-terminally-mutated Tar and Tcp expressed in a receptorless E. coli strain mediated responses to aspartate and citrate, respectively, but their adaptation abilities were severely impaired. Their expression levels and attractant-sensing abilities were similar to those of the wild-type receptors, but the methylation levels of the mutant receptors increased only slightly upon addition of attractants. When CheR was overproduced, both the adaptation and methylation profiles of the mutant Tar receptor became comparable to those of wild-type Tar. Furthermore, overproduction of CheR also enhanced adaptive methylation of wild-type Trg, which lacks the NWETF sequence, in the absence of any other chemoreceptor. These results suggest that the pentapeptide sequence facilitates effective adaptation and methylation by recruiting CheR.

Adaptation, Physiological↗
PubMed2002

Degradation of a Caulobacter soluble cytoplasmic chemoreceptor is ClpX dependent.

In order to determine whether ClpXP-mediated proteolysis is a common mechanism used to regulate the chemotaxis machinery during the cell cycle of Caulobacter crescentus, we have characterized a soluble cytoplasmic chemoreceptor, McpB. The mcpB gene lies adjacent to the major chemotaxis operon, which encodes 12 chemotaxis proteins, including the membrane chemoreceptor McpA. Like McpA, McpB possesses a C-terminal CheBR docking motif and three potential methylation sites, which we suggest are methylated. The McpB protein is degraded via a ClpX-dependent pathway during the swarmer-to-stalked cell transition, and a motif, which is 3 amino acids N-terminal to the McpB CheBR docking site, is required for proteolysis. Analysis of the degradation signal in McpB and McpA reveals a common motif present in the other four chemoreceptors that possess CheBR docking sites. A green fluorescent protein (GFP) fusion bearing 58 amino acids from the C terminus of McpA, which contains this motif, is degraded, suggesting that the C-terminal sequence is sufficient to confer ClpXP protease susceptibility.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1994

Do carotid chemoreceptors inhibit the hyperventilatory response to heavy exercise?

In this paper two types of evidence are presented which question the commonly presumed role of carotid chemoreceptor stimulation as the primary mediator of the hyperventilatory response to heavy exercise. First, carotid-body denervation in ponies increases their hyperventilatory response to heavy exercise. Second, the awake dog and the goat at rest show an immediate and substantial depression of tidal volume and of ventilation when their isolated carotid chemoreceptors are made hypocapnic. Accordingly, it is proposed that during heavy exercise the carotid chemoreceptors are inhibitory to respiratory motor output and that the cause of the hyperventilatory response originates from extrachemoreceptor, locomotor-linked, feed-forward stimuli.

Animals↗
PubMed1984

The role of aortic chemoreceptors during acute anemia.

The importance of aortic chemoreceptors in the circulatory and metabolic responses during acute anemia was studied in anesthetized dogs. Data were obtained from nine dogs in which the aortic chemoreceptors were surgically denervated prior to induction of anemia, and from seven sham-operated dogs. Cardiac output (QT), limb blood flow (QL), limb and whole body oxygen uptake (VO2) were determined at normal hematocrit (Hct) and at 30 min of anemia (Hct = 13%) produced by isovolemic dextran-for-blood exchange. At 30 min of anemia, QT was increased from 91 to 186 mL . kg-1 . min-1 (p less than 0.01) and from 99 to 153 mL . kg-1 . min-1 (p less than 0.01) in the sham and denervated groups, respectively. The increase in QT during anemia was less (p less than 0.05) in the aortic-denervated series. Limb flow was also increased during anemia in both groups (p less than 0.01); the mean value of 89 mL . kg-1 . min-1 in the denervated group was less than that of 130 mL . kg-1 . min-1 observed in the sham animals (p less than 0.05). Whole body VO2 decreased (p less than 0.05) in the denervated group at 30 min of anemia; limb VO2 was maintained at the preanemic control value in both groups. The data indicate that during acute anemia the aortic chemoreceptors contribute to the increase in QT.

Acute Disease↗
PubMed1985

The role aortic chemoreceptors during severe CO hypoxia.

The importance of aortic chemoreceptors in the circulatory responses to severe carbon monoxide (CO) hypoxia was studied in anesthetized dogs. The aortic chemoreceptors were surgically denervated in eight dogs prior to the induction of CO hypoxia, with nine other dogs serving as intact controls. Values for both whole body and hindlimb blood flow, vascular resistance, and O2 uptake were determined prior to and at 30 min of CO hypoxia in the two groups. Arterial O2 content was reduced 65% using an in situ dialysis method to produce CO hypoxia. At 30 min of hypoxia, cardiac output increased but limb blood flow remained at prehypoxic levels in both groups. This indicated that aortic chemoreceptor input was not necessary for the increase in cardiac output during severe CO hypoxia, nor for the diversion of this increased flow to nonmuscle tissues. Limb O2 uptake decreased during CO hypoxia in the aortic-denervated group but remained at prehypoxic levels in the intact group. The lower resting values for limb blood flow in the aortic-denervated animals required a greater level of O2 extraction to maintain resting O2 uptake. When CO hypoxia was superimposed upon this compensation, an O2 supply limitation occurred because the limb failed to vasodilate even as maximal levels for O2 extraction were approached.

Animals↗
PubMed1992

Characterization of cultured chemoreceptor cells dissociated from adult rabbit carotid body.

Short-term cell cultures were obtained from enzymatically dissociated carotid bodies from adult rabbits, and morphological and functional characterization of the cultured chemoreceptor cells were carried out. Under phase contrast, freshly isolated type I cells are round, bright, and 10-14 microns in diameter and exhibit strong fluorescence when stained with the glyoxylic acid technique. The content of endogenous dopamine in the cultures increased from 80 pmol/10(5) cells 2 h after plating the cells to 200 pmol/10(5) cells on the 3rd day, and the rate of synthesis and storage of [3H]dopamine from the precursor [3H]tyrosine increased from 1.7 pmol.10(5) cells-1.h-1 in 1-day cultures to 4 pmol.10(5) cells-1.h-1 on the 3rd day; the later values represent 80-85% of the expected values for the intact carotid body. After labeling with [3H]tyrosine, cultured chemoreceptor cells release [3H]dopamine when challenged by hypoxia, high external K+, or the protonophore dinitrophenol, the pattern of response being similar to that of the intact carotid body. When studied by whole cell clamp recording, individual chemoreceptor cells exhibit a marked variability in the properties of some ionic currents; the data, however, do not support the existence of distinct subpopulations of type I cells.

Animals↗
PubMed1994

Participation of Na+ channels in the response of carotid body chemoreceptor cells to hypoxia.

The role played by Na+ channels of carotid body (CB) chemoreceptor cells was investigated by studying the effects of tetrodotoxin (TTX) on the release of 3H-labeled catecholamines ([3H]CA) by adult rabbit CBs previously incubated with the precursor [3H]tyrosine. TTX inhibited partially the release of [3H]CA elicited by mild hypoxia (10 or 7% O2) or by depolarizing incubation medium containing 20 or 30 mM KCl, but the response to more intense hypoxia (5 or 2% O2) or to higher KCl concentration (40 or 50 mM) was not significantly affected. The release of [3H]CA elicited by acidic stimuli, either 20% CO2 (pH 6.6) or the protonophore dinitrophenol (100 microM), although comparable in magnitude to that elicited by mild hypoxia, was not modified by TTX. These results provide evidence for the first time that Na+ channels of chemoreceptor cells participate in the transduction of hypoxic stimuli into the neurotransmitter release response of these cells and suggest that Na+ current operates as an amplifying device that enhances the initial cell depolarization mediated by the closure of the O2-sensitive K+ channels. Sympathetic denervation of CBs was followed by a marked reduction in the release of [3H]CA elicited by veratridine or by 20 mM KCl, suggesting that the number of Na+ channels in chemoreceptor cells decreases after denervation.

Acids↗