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PubMed1988

Physiology of chemoreceptor cells in the legs of the freshwater prawn, Macrobrachium rosenbergii.

1. Chemoreceptor cells in the first pereiopods (legs) of the freshwater prawn, Macrobrachium rosenbergii, were investigated using single-unit, extracellular electrophysiological recording techniques on an isolated, perfused leg preparation. 2. The cells were responsive to aqueous extracts of food (shrimp, mullet, trout chow), a salt mixture (artificial sea-water), amino acids (L-arginine HCl, taurine), a quaternary ammonium compound (betaine HCl) and ammonium chloride. 3. The response specificity of individual cells ranged from narrow to broad, but on average was broad, being more similar to chemoreceptor cells of freshwater crayfish than of marine spiny or clawed lobsters. 4. Responses were generally excitatory. However, some responses were inhibitory, the first such demonstration in aquatic crustaceans. 5. These electrophysiological results highly correlate with results of feeding behavioral assays carried out on M. rosenbergii.

Animals↗
PubMed1981

Sympathectomy does not alter the response of carotid chemoreceptors to hypoxemia during carboxyhemoglobinemia or anemia.

We tested the effects of section of the sympathetic innervation to the carotid body on the responses of single carotid chemoreceptor fibers to carboxyhemoglobinemia (40-50%) and anemia (15-20% Hct) at various levels of paO2 (range: 20-450 Torr). Sympathectomy had virtually no effect on the steady-state response curves of carotid chemoreceptors to O2, either in normal cats or in those with reduced oxygen transport due to anemia or carboxyhemoglobinemia.

Action Potentials↗
PubMed1983

Inhibition in carotid body chemoreceptors mediated by D-2 dopaminoceptors: antagonism by benzamides.

Inhibition of chemosensory nerve impulses in the cat is evoked by dopamine (DA) applied to carotid body chemoreceptors. Pharmacological characterization of the dopaminoceptors involved in this action was determined through their blockade with benzamides, selective antagonists of D-2 receptors. Both metoclopramide and sulpiride were effective blockers of DA-induced chemosensory inhibition. Furthermore, both drugs induced an immediate increase in the frequency of carotid nerve chemosensory impulses, suggesting the presence of previous tonic inhibition of chemoreceptor discharges by endogenous DA released from glomus cells.

Animals↗
PubMed1983

In vitro recording of chemoreceptor activity in catecholamine-depleted rabbit carotid bodies.

Carotid bodies, together with Hering's nerves, were excised from anesthetized rabbits 24, 48 or 72 h after single reserpine injections (5 mg kg-1, i.v. or i.p.) and were superfused in vitro. Some carotid bodies were processed for formaldehyde-induced fluorescence microscopy to assess catecholamine depletion. Twenty-four hours after reserpine treatment, most of the type I cell islets had lost their fluorescence and the number of spontaneously active chemoafferent units was dramatically reduced. Forty-eight hours after reserpine injection, both the fluorescence of type I cells had partially recovered and the number of chemoreceptor units was almost normal. A significant reduction of both the normoxic and hypoxic frequencies of discharge was demonstrated in carotid bodies examined 24 or 48 h after reserpine pretreatment. Superfusions with dopamine (1, 10, 100 microM) transiently restored the response to hypoxia. It is proposed that catecholamines contained in type I cells play a prominent role in the genesis of chemoafferent activity and in the chemoreceptor response to hypoxia.

Animals↗
PubMed1992

Chemoreceptor A-fibres in the human carotid body contain tyrosine hydroxylase and neurofilament immunoreactivity.

Previous retrograde tracing studies on rat and guinea-pig showed a projection of sensory tyrosine hydroxylase-immunoreactive neurons to the region of the carotid bifurcation via the carotid sinus nerve. In the present study, focussing on the sensory innervation of the human carotid body, antisera to tyrosine hydroxylase and other catecholamine synthesizing enzymes were applied for an immunohistochemical investigation of carotid bodies obtained at autopsy. In addition, an array of antisera directed to non-enzyme antigens known to be present in viscero-afferent neurons were incorporated in the study. The glomic lobules consisting of glomus cells and sustentacular cells contained a variable number of enzyme-immunoreactive glomus cells. Arteries were supplied by nerve fibres displaying the full phenotype of sympathetic noradrenergic axons, i.e. immunoreactivity to tyrosine hydroxylase, aromatic-L-amino-acid-decarboxylase and dopamine-beta-hydroxylase. The glomic lobules, however, were densely innervated by tyrosine hydroxylase-immunoreactive axons lacking immunoreactivity to aromatic-L-amino-acid-decarboxylase and dopamine-beta-hydroxylase. These fibres reacted with neurofilament 160kD-antibody but were devoid of immunoreactivity to all neuropeptides tested (calcitonin gene-related peptide, somatostatin, substance P). Ultrastructurally, tyrosine hydroxylase/neurofilament 160kD-immunoreactive axons gave rise to large axonal swellings filled with mitochondria and vesicles, and established extensive contacts to glomus cells. Nerve bundles surrounded by a perineural sheath contained both myelinated (2.0-2.8 microns in diameter) and unmyelinated (0.14-3.0 microns) tyrosine hydroxylase-immunoreactive axons. Most of the unmyelinated immunoreactive axons were running singularly within a Schwann cell-sheath. Judged from the pattern of immunoreactivities as well as their preterminal and terminal ultrastructure, tyrosine hydroxylase-immunoreactive axons innervating glomus cells are of sensory origin. Although final proof by retrograde tracing cannot be presented in man, this conclusion is supported by experimental evidence in laboratory animals. The myelinated immunoreactive axons correspond to chemoreceptor A-fibres whereas the classification of the large unmyelinated immunoreactive axons has yet to be established. The lack of immunoreactivity to the dopamine-synthesizing enzyme, aromatic-L-amino-acid-decarboxylase, in this fibre type does not support the view of dopamine being the primary transmitter of chemoreceptor afferents.

Aged↗
PubMed2004

Detection of hypoxia-evoked ATP release from chemoreceptor cells of the rat carotid body.

The carotid body (CB) is a chemosensory organ that detects changes in chemical composition of arterial blood and maintains homeostasis via reflex control of ventilation. Thus, in response to a fall in arterial PO(2) (hypoxia), CB chemoreceptors (type I cells) depolarize, and release neurotransmitters onto afferent sensory nerve endings. Recent studies implicate ATP as a key excitatory neurotransmitter released during CB chemoexcitation, but direct evidence is lacking. Here we use the luciferin-luciferase bioluminescence assay to detect ATP, released from rat chemoreceptors in CB cultures, fresh tissue slices, and whole CB. Hypoxia evoked an increase in extracellular ATP, that was inhibited by L-type Ca(2+)channel blockers and reduced by the nucleoside hydrolase, apyrase. Additionally, iberiotoxin (IbTX; 100 nM), a blocker of O(2)-sensitive Ca(2+)-dependent K(+) (BK) channels, stimulated ATP release and largely occluded the effect of hypoxia. These data strongly support a neurotransmitter role for ATP in carotid body function.

Adenosine Triphosphate↗
PubMed2006

Physiological and behavioral effects of chemoreceptors located in different body parts of the swimming crab Callinectes danae.

By perfusing their branchial chambers with filtered seawater, we have developed a preparation that allows us to maintain the swimming crab Callinectes danae outside water without any major effects on its cardiac activity. This in turn allowed us to selectively stimulate chemoreceptors located in different body parts, and specifically to discriminate between the receptors located in the branchial chambers and those located in the oral region (mainly in the mouthparts, antennules and antennae). We show that a taurine solution can evoke bradycardia when applied to the oral region or to a combination of the oral region and the branchial chambers. Although the precise localization of the oral region receptors involved remains to be determined, ablation experiments show that the olfactory organs (i.e., the antennules) are not involved. Finally, we show that although stimulating the pereiopods has no effect on the animals' cardiac activity it causes the animals to move, putatively to try to grasp a piece of food, a reaction not evoked by stimulating the gills or the oral regions. Our results lend support to the idea that chemoreceptors located in different parts of the body play different functional roles in decapod crustaceans.

Animals↗
PubMed2005

An evaluation of cobalt chloride as an O2-sensitive chemoreceptor stimulant in channel catfish.

The effects of cobalt chloride on heart rate, blood pressure, ventilatory frequency and opercular pressure amplitude in channel catfish, Ictalurus punctatus were measured to evaluate the potential of cobalt as a histochemical probe to study mechanisms of oxygen chemoreception, as well as assess the general effects of cobalt on the cardioventilatory physiology of fishes. Cobalt, like cyanide, has been previously used to stimulate oxygen chemoreceptors and hypoxic reflexes in mammals but there is little information on the cardioventilatory effects of cobalt on fish. Catfish were exposed to increasing concentrations (1-20 mg/kg) of cobalt in the water (external) or injections into the dorsal aorta (internal) and the cardioventilatory effects recorded. Mean arterial pressure showed a significant, dose-dependent increase in response to cobalt injections. Heart rate increased slowly, but significantly after cobalt injections but the magnitude of change was not dose-dependent. There was a small increase in ventilatory rate but no effect on amplitude. External cobalt had similar effects but the responses were weaker. Although cobalt stimulated some cardioventilatory reflexes the pattern and magnitude of the responses were noticeably different from those of cyanide and hypoxia. The results suggest that the cardioventilatory reflexes stimulated by cobalt were not mediated by O(2)-sensitive chemoreceptors and that cobalt is not an effective O(2) receptor stimulant in fishes.

Animals↗
PubMed2006

The link between carotid artery disease and ischemic stroke may be partially attributable to autonomic dysfunction and failure of cerebrovascular autoregulation triggered by Darwinian maladaptation of the carotid baroreceptors and chemoreceptors.

Carotid artery stenosis is generally thought to induce stroke by either compromising cerebral perfusion or inciting embolic phenomena. Carotid baroreceptors and chemoreceptors are vital adaptations for cerebrovascular autoregulation that can behave mal-adaptively in the setting of modern diseases such as atherosclerosis. We hypothesize that acute cerebrovascular events may be partially attributable to autonomic dysfunction and cerebrovascular autoregulatory failure secondary to carotid sensor maladaptations. Specifically, we propose that atherosclerotic disease at the carotid bifurcation can interfere with baroreceptor and chemoreceptor function by buffering against accurate detection of physical and chemical parameters. Misperceptions of hypoxia and hypotension can trigger sympathetic bias and autonomic dysfunction which perturb cerebrovascular autoregulation and vasomotor tone, thereby compromising cerebral perfusion. The preferential association of strokes with morning arousal, stress, acute physical activity, winter months, illness, and older age may relate to this phenomenon. Sympathetic bias promotes inflammation and coagulation, a link likely forged during prehistoric evolution when trauma represented a more significant factor in natural selection. In the setting of carotid sensor dysfunction, the resulting inflammation and coagulation can promote acute cardiovascular events. The ensuing cerebral ischemia can induce further derangement of cerebrovascular autoregulation and upregulate adrenergia, inflammation, and coagulation in a feed-forward manner. Inflammation and coagulation can also exacerbate carotid sensor dysfunction by iteratively worsening atherosclerosis. Angioplasty, stenting, and endarterectomy may inadvertently cause acute and chronic carotid sensor dysfunction through manipulation, material interposition, and balloon-induced baroreceptor injury. Acute strokes during these procedures may result from carotid sensor dysfunction rather than embolization. Carotid body and sinus electro-modulation and non-balloon atherectomy represent new methods to prevent or treat cerebrovascular events. Pharmacologic modulation of autonomic balance, such as adrenergic blockade, long presumed contraindicated due to risk of cerebral hypoperfusion, may counter-intuitively offer benefit during acute strokes. Novel diagnostic paradigms may include functional analysis of carotid sensors as well as measurement of the anatomic thickness of calcified and non-calcified plaque near the carotid body. Carotid sensor dysfunction may be a source of systemic sympathetic bias and autonomic dysfunction observed during aging and, by association, many of the ailments associated with senescence. Modulation of carotid sensors may yield pervasive health benefits beyond those found by treating cerebrovascular disease.

Adaptation, Physiological↗
PubMed2004

CO2 transduction mechanisms in avian intrapulmonary chemoreceptors: experiments and models.

Intrapulmonary chemoreceptors (IPC) are neurons that sense tonic and phasic CO2 stimuli in the lungs of birds and diapsid reptiles. IPC are different from most other vertebrate respiratory CO2 receptors because: (1) they are stimulated by low PCO2 and inhibited by high PCO2, (2) they have extremely rapid response characteristics, (3) their CO2 sensitivity is nearly abolished by intracellular inhibitors of carbonic anhydrase, and (4) their CO2 sensitivity is strongly depressed by inhibiting Na+/H+ antiport exchange. Experimental evidence suggests that IPC respond to intracellular pH, not CO2 directly, and that intracellular pH and IPC discharge are determined by a kinetic balance between CO2 hydration/dehydration rates, transmembrane acid/base exchange rates, and intracellular buffering. We review experimental evidence for and against various mechanisms of IPC CO2 chemotransduction, present a conceptual and mathematical model of the proposed mechanisms, and compare this model to CO2 transduction in other respiratory chemoreceptors.

Action Potentials↗
PubMed2003

Characterization of nicotinic acetylcholine receptors in cultured arterial chemoreceptor cells of the cat.

Neurotransmitters appear to be involved in chemotransmission of the carotid body, a major arterial chemoreceptor. Substantial data indicate that acetylcholine (ACh) is an excitatory neurotransmitter in the carotid body, regulating the excitability of afferent nerve endings and glomus cells (putative chemoreceptor cells). In this study we characterized properties of nicotinic ACh receptors (nAChRs) in cultured cat glomus cells using immunocytochemistry and whole cell patch clamp techniques. Cultured glomus cells expressed immunoreactivity for alpha3, alpha4, and beta2 subunits of nAChRs. An application of ACh elicited inward current. Nicotinic AChRs of glomus cells showed high affinity for ACh. The current-voltage relationship showed strong inward rectification at positive membrane potential. alpha-Conotoxin MII (20 nM), dihydro-beta-erythroidine (DHbetaE; 1 nM), and hexamethonium (300 microM) significantly inhibited ACh-induced current. These results indicate that cultured cat glomus cells possess functional nAChRs, and that their characteristics are consistent with those of alpha3, alpha4 and beta2 containing nAChRs.

Acetylcholine↗
PubMed2003

Transmembrane organization of the Bacillus subtilis chemoreceptor McpB deduced by cysteine disulfide crosslinking.

The Bacillus subtilis chemoreceptor McpB is a dimer of identical subunits containing two transmembrane (TM) segments (TM1, residues 17-34: TM2, residues 280-302) in each monomer with a 2-fold axis of symmetry. To study the organization of the TM domains, the wild-type receptor was mutated systematically at the membrane bilayer/extracytoplasmic interface with 15 single cysteine (Cys) substitutions in each of the two TM domains. Each single Cys substitution was capable of complementing a null allele in vivo, suggesting that no significant perturbation of the native tertiary or quaternary structure of the chemoreceptor was introduced by the mutations. On the basis of patterns of disulfide crosslinking between subunits of the dimeric receptor, an alpha-helical interface was identified between TM1 and TM1' (containing residues 32, 36, 39, and 43) and between TM2 and TM2' (containing residues 276, 277, 280, 283 and 286). Pairs of cysteine substitutions (positions 34/280 and 38/273) in TM1 and TM2 were used to further elucidate specific contacts within a monomer subunit, enabling a model to be constructed defining the organization of the TM domain. Crosslinking of residues that were 150-180 degrees removed from position 32 (positions 37, 41, and 44) suggested that the receptors may be organized as an array of trimers of dimers in vivo. All crosslinking was unaffected by deletion of cheB and cheR (loss of receptor demethylation/methylation enzymes) or by deletion of cheW and cheV (loss of proteins that couple receptors with the autophosphorylating kinase). These findings indicate that the organization of the transmembrane region and the stability of the quaternary complex of receptors are independent of covalent modifications of the cytoplasmic domain and conformations in the cytoplasmic domain induced by the coupling proteins.

Bacillus subtilis↗
PubMed1998

Further characterization of stimulus interaction of cat carotid chemoreceptors.

The hypothesis that the maximal response to pCO2 of carotid body chemoreceptors would be the same regardless of pO2, if the receptor molecule behaves like a hemoglobin molecule, was investigated using single or a few fiber carotid body chemoreceptors in cats in vivo which were anesthetized and artificially ventilated. In one series, graded levels of CO2 inhalation in steady-state at p(a)O2 = 354 +/- 19 Torr showed a linear response from 1 to 20.1 +/- 2.3 imp/s for p(a)CO2 increase from 32 to 178 +/- 18 Torr, and at p(a)O2 of 48 +/- 3.8 Torr, from 3.8 to 18.6 +/- 1.7 imp/s for p(a)CO2 increase from 21 to 109 +/- 11 Torr, levelling off thereafter. In another series of multi-fiber preparation, close intra-arterial injection of blood plus saline containing pCO2 of about 270 Torr gave peak responses of 44 +/- 9, 42 +/- 6 and 42 +/- 7 imp/s at p(a)O2 of 40 +/- 4, 82 +/- 6 and 388 +/- 18 Torr, respectively. Thus, the chemosensory responses to p(a)CO2 reached the same level of maximal activity regardless of p(a)O2. Taken together, the maximal responses in both steady-state and transient-state to p(a)CO2 appeared to be the same at hypoxic and hyperoxic p(a)O2. This stimulus-response relationship of the receptor molecule is analogous to O2-CO2 interaction with hemoglobin molecule with a Bohr effect, reaching a saturation point at a finite pO2.

Acidosis↗
PubMedDate not supplied

Selectivity of chemoreceptor neuron.

Discriminating ability (selectivity) of chemoreceptor neuron is compared with that of its receptor proteins. The process of neuronal triggering is expected to be cooperative and threshold-type in a sense that the neuron can fire if and only if the number of its receptor proteins, which are bound with odor molecules, is above a definite threshold. Both deterministic and stochastic pictures are considered. The stochastic case is treated based on birth and death stochastic process and first passage technique. In both pictures, it is shown that a chemoreceptor neuron can have much a higher selectivity than its individual receptor proteins, provided the chemical stimuli are presented at low concentrations, and the threshold is high enough. This is in agreement with a preliminary estimate based on simplified probabilistic reasoning (Vidybida, A.K., 1999. Cooperative mechanism for improving the discriminating ability in the chemoreceptive neuron. Binomial case. Biol. Cybern. 81, 469-473). The mechanism of selectivity improvement is similar to that described before in cooperative chemical systems. A possibility for this mechanism to be valid at higher stages of processing of chemical signals, as well as in other sensory systems is discussed.

Chemoreceptor Cells↗
PubMed2002

Chronic hypoxia remodels voltage-gated Ca2+ entry in a human airway chemoreceptor cell line.

Arterial and airway chemoreceptors respond to acute hypoxia by depolarizing, thereby activating voltage-gated Ca2+ channels and so permitting Ca2+ entry to trigger transmitter release. Following periods of prolonged hypoxia, these cells undergo a form of remodelling which involves altered expression of ion channels. Here, we use microspectrofluorimetric recordings of voltage-gated Ca2+ entry (activated by exposure of cells to 50 mM K+) to show that chronic hypoxia suppresses such Ca2+ entry in model airway chemoreceptor (H146) cells. Furthermore, Ca2+ entry via L-type channels is suppressed, whilst entry via N-type channels is greatly enhanced. The suppressed response, together with dramatic remodelling of routes available for voltage-gated Ca2+ entry, is likely to alter significantly the acute O2 sensing properties of these cells.

Calcium↗
PubMed1997

Renal R2 chemoreceptor activity is attenuated after back heating in the rat.

Recent study in our laboratory has found that renal afferent nervous activity (RANA) was decreased during and after 42 degrees C back heating (BH). To investigate which renal sensory receptor is influenced during and after BH, a C-shaped glass heating pad (42 degrees C) was used on the skin of the back overlying the kidneys. A single-unit recording was used to identify four types of renal sensory receptors, the R2 chemoreceptor (CR2), arterial mechanoreceptor (MRa), ureteropelvic mechanoreceptor (MRu) and venous mechanoreceptor (MRv) in anesthetized female Wistar rats. Renal cortical microvascular blood flow (CMBF) and urinary water, potassium and sodium output were measured. It was found that CR2 activity was significantly decreased during and after BH, but three types of MRs were not altered. CMBF and urine output were significantly increased during and after BH. It is concluded that the increase in renal hemodynamics by BH may dilute some chemicals in the kidney and decrease the firing rate of R2 chemoreceptors.

Animals↗
PubMed2001

Properties of solitary tract neurones responding to peripheral arterial chemoreceptors.

Despite the highly integrated pattern of response evoked by peripheral chemoreceptor stimulation, limited information exists regarding the neurones within the nucleus of the solitary tract that mediate this reflex. Using a working heart-brainstem preparation, we describe evoked synaptic response patterns, some intrinsic membrane properties, location, morphology and axonal projections of physiologically characterised 'chemoreceptive' neurones located in the solitary tract nucleus in the rat. From 172 whole cell recordings, 56 neurones were identified as chemoreceptive since they responded to aortic injections of low doses of sodium cyanide (2-5 microg). Chemoreceptive neurones had a mean resting membrane potential of -52+/-1 mV and input resistance was 297+/-15 M(Omega) (n=56). Synaptic responses evoked included excitatory synaptic potentials alone, excitatory-inhibitory post-synaptic potential complexes, inhibitory synaptic potentials alone and central respiratory modulated synaptic potentials. Synaptic response latency data were obtained by stimulating electrically the solitary tract: the mean excitatory synaptic latency was 5.2+/-0.4 ms (range 2.5-8.0 ms; n=17). Chemoreceptive neurones showed a heterogeneity in their intrinsic membrane properties: neurones displayed either steady state, augmenting or adapting firing responses to depolarising current injection and, in some neurones, either delayed excitation or rebound activity following hyperpolarising pulses. Eleven chemoreceptive neurones were labelled and provided the first morphological data of these cells. Labelled somata were detected dorsomedial or medial to the solitary tract spanning the obex. Neurones typically had three to eight primary dendrites which often entered the solitary tract as well as extending across the ipsilateral region of the nucleus of the solitary tract. Axons were mostly unmyelinated with boutons of the en passant variety and often ramified within the solitary tract nucleus as well as coursed towards the ipsilateral ventral medulla. In summary, this study provides new data on the neurophysiological, anatomical and morphological properties of nucleus of the solitary tract neurones responding to arterial chemoreceptors in the rat.

Action Potentials↗
PubMed1992

Partial characterization and detergent solubilization of the putative glutathione chemoreceptor from hydra.

Feeding behavior in hydra is initiated by the association of glutathione (GSH) with a putative external chemoreceptor. In the present study, the binding of [35S]GSH to hydra membranes has been characterized. Nondisplaceable [35S]GSH binding which compromised previous analyses [Grosvenor, W., Bellis, S., Kass-Simon, G., & Rhoads, D. (1992) Biochim. Biophys. Acta (in press)] was eliminated by treating membranes with an inhibitor of GSH metabolism, borate in combination with L-serine. The specific binding which was not inhibited by borate/serine demonstrated many of the characteristics expected of a ligand/receptor interaction. The binding was rapid, reversible, and saturable. A Scatchard analysis of saturation isotherms indicated a dissociation constant (KD) of 3.4 microM, a value which is in good agreement with concentrations of glutathione which are known to induce feeding behavior. Hydra membranes were detergent-solubilized with 10 mM 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), 100 mM KCl, and 10% glycerol. The soluble fraction contained 40% of the original saturable, reversible GSH binding activity. The KD for GSH binding to the solubilized preparation was estimated as 2.7 microM, a valuable which is not appreciably different from the KD for binding to intact membranes. The fidelity of GSH binding in the solubilized preparation suggests that this preparation will be useful in further characterization of the putative glutathione chemoreceptor.

Animals↗