scholarly journals pH regulation in adult rat carotid body glomus cells. Importance of extracellular pH, sodium, and potassium.

1992 ◽  
Vol 100 (4) ◽  
pp. 593-608 ◽  
Author(s):  
T J Wilding ◽  
B Cheng ◽  
A Roos
Keyword(s):  
Carotid Body ◽  
Ph Regulation ◽  
Type I ◽  
Glomus Cell ◽  
Strong Base ◽  
Glomus Cells ◽  
Adult Rat ◽  
High K ◽  
Buffering Power ◽  
I Cells

The course of intracellular pH (pHi) was followed in superfused (36 degrees C) single glomus (type I) cells of the freshly dissociated adult rat carotid body. The cells had been loaded with the pH-sensitive fluorescent dye 2',7'-(2-carboxyethyl)-5 (and -6)-carboxyfluorescein. The high K(+)-nigericin method was used for calibration. The pHi of the glomus cell at pHo 7.40, without CO2, was 7.23 +/- 0.02 (n = 70); in 5% CO2/25 mM HCO3-, pHi was 7.18 +/- 0.08 (n = 9). The pHi was very sensitive to changes in pHo. Without CO2, delta pHi/delta pHo was 0.85 (pHo 6.20-8.00; 32 cells), while in CO2/HCO3- this ratio was 0.82 irrespective of whether pHo (6.80-7.40; 14 cells) was changed at constant PCO2 or at constant [HCO3-]o. The great pHi sensitivity of the glomus cell to pHo is matched only by that of the human red cell. An active Na+/H+ exchanger (apparent Km = 58 +/- 6 mM) is present in glomus cells: Na+ removal or addition of the amiloride derivative 5-(N,N-hexamethylene)-amiloride induced pHi to fall by as much as 0.9. The membrane of these cells also contains a K+/H+ exchanger. Raising [K+]o from 4.7 to 25, 50, or 140 mM reversibly raised pHi by 0.2, 0.3, and 0.6, respectively. Rb+ had no effect, but in corresponding concentrations of Tl+ alkalinization was much faster than in K+. Reducing [K+]o to 1.5 mM lowered pHi by 0.1. These pHi changes were shown not to be due to changes in membrane voltage, and were even more striking in the absence of Na+. Intrinsic buffering power (amount of strong base required to produce, in the nominal absence of CO2, a small pHi rise) increased from 3 to approximately 21 mM as pHi was lowered, but remained nearly unchanged below pHi 6.60. The fitted expression assumed the presence of one "equivalent" intracellular buffer (pK 6.41, 41 mM). The exceptional pHi sensitivity to pHo suggests that the pHi of the glomus cell is a link in the chemoreceptor's response to external acidity.

Enhanced adenosine A2breceptor signaling facilitates stimulus-induced catecholamine secretion in chronically hypoxic carotid body type I cells

2013 ◽  
Vol 305 (7) ◽  
pp. C739-C750 ◽  
Author(s):  
Simon Livermore ◽  
Colin A. Nurse
Keyword(s):  
Carotid Body ◽  
Catecholamine Secretion ◽  
Receptor Blocker ◽  
Type I ◽  
Dependent Manner ◽  
Body Type ◽  
Type I Cells ◽  
High K ◽  
Sch 58261 ◽  
I Cells

Chronic hypoxia (CHox) augments chemoafferent activity in sensory fibers innervating carotid body (CB) chemoreceptor type I cells; however, the underlying mechanisms are poorly understood. We tested the hypothesis that enhanced paracrine signaling via adenosine (Ado) A2breceptors is involved. Dissociated rat CB cultures were exposed for 24 h to normoxia (Nox, 21% O2) or CHox (2% O2) or treated with the hypoxia mimetic deferoxamine mesylate (DFX), and catecholamine secretion from type I cells was monitored by amperometry. Catecholamine secretion was more robust in CHox and DFX type I cells than Nox controls after acute exposure to acid hypercapnia (10% CO2, pH 7.1) and high K+(75 mM). Exogenous Ado increased catecholamine secretion in a dose-dependent manner, and the EC50was shifted to the right from ∼21 μM Ado in Nox cells to ∼78 μM in CHox cells. Ado-evoked secretion in Nox and CHox cells was markedly inhibited by MRS-1754, an A2breceptor blocker, but was unaffected by SCH-58261, an A2areceptor blocker. Similarly, MRS-1754, but not SCH-58261, partially inhibited high-K+-evoked catecholamine secretion, suggesting a contribution from paracrine activation of A2breceptors by endogenous Ado. CB chemostimuli, acid hypercapnia, and hypoxia elicited a MRS-1754-sensitive rise in intracellular Ca2+that was more robust in CHox and DFX than Nox cells. Taken together, these data suggest that paracrine Ado A2breceptor signaling contributes to stimulus-evoked catecholamine secretion in Nox and CHox CB chemoreceptors; however, the effects of Ado are more robust after CHox.

Transduction mechanisms in carotid body: glomus cells, putative neurotransmitters, and nerve endings

1980 ◽  
Vol 239 (5) ◽  
pp. C135-C152 ◽  
Author(s):  
C. Eyzaguirre ◽  
S. J. Fidone
Keyword(s):  
Carotid Body ◽  
Conclusive Evidence ◽  
Sensory Transduction ◽  
Nerve Endings ◽  
High Pco2 ◽  
Type I ◽  
Glomus Cell ◽  
Impulse Frequency ◽  
Glomus Cells ◽  
Carotid Body Chemoreceptors

Carotid body chemoreceptors are activated by low PO2, high PCO2, acidity, increased temperature, and tonicity. These receptors are important in homeostasis and mediate their reflex effects on the CNS through sensory discharges of the carotid (sinus) nerve. The receptor complex is formed by glomus (type I) cells and carotid nerve endings, which, morphologically, appear to form a sensory synapse. The junction between glomus cells and nerve endings is enveloped by processes of sustentacular (type II) cells. The mechanisms of chemoreceptor transduction are complex; there is no agreement about the identity of the primary receptor element (glomus cell or nerve terminal) or what mechanisms are responsible for the onset of the sensory discharge in the carotid nerve. There is increasing evidence that integrity of the glomus cell is essential for normal transduction and that the receptor synapse described by morphologists may be functionally active. There is no conclusive evidence, however, that the glomus cell is the primary site of sensory transduction. Stimuli act on the glomus cell to release "transmitter" and/or "modulator" substances; but it is unknown if the released chemicals are directly responsible for the accompanying change in sensory impulse frequency or merely modify an already ongoing discharge. Interactions between glomus cells and nerves may be complicated enough to make it very difficult to resolve this question.

Autocrine and paracrine actions of ATP in rat carotid body

2012 ◽  
Vol 90 (6) ◽  
pp. 705-711 ◽  
Author(s):  
Amy Tse ◽  
Lei Yan ◽  
Andy K. Lee ◽  
Frederick W. Tse
Keyword(s):  
Carotid Body ◽  
Cellular Damage ◽  
Type I ◽  
Glomus Cells ◽  
Sustentacular Cells ◽  
Arterial Blood ◽  
Carotid Bodies ◽  
Intracellular Ca ◽  
Paracrine Actions ◽  
I Cells

Carotid bodies are peripheral chemoreceptors that detect lowering of arterial blood O2 level. The carotid body comprises clusters of glomus (type I) cells surrounded by glial-like sustentacular (type II) cells. Hypoxia triggers depolarization and cytosolic [Ca2+] ([Ca2+]i) elevation in glomus cells, resulting in the release of multiple transmitters, including ATP. While ATP has been shown to be an important excitatory transmitter in the stimulation of carotid sinus nerve, there is considerable evidence that ATP exerts autocrine and paracrine actions in carotid body. ATP acting via P2Y1 receptors, causes hyperpolarization in glomus cells and inhibits the hypoxia-mediated [Ca2+]i rise. In contrast, adenosine (an ATP metabolite) triggers depolarization and [Ca2+]i rise in glomus cells via A2A receptors. We suggest that during prolonged hypoxia, the negative and positive feedback actions of ATP and adenosine may result in an oscillatory Ca2+ signal in glomus cells. Such mechanisms may allow cyclic release of transmitters from glomus cells during prolonged hypoxia without causing cellular damage from a persistent [Ca2+]i rise. ATP also stimulates intracellular Ca2+ release in sustentacular cells via P2Y2 receptors. The autocine and paracrine actions of ATP suggest that ATP has important roles in coordinating chemosensory transmission in the carotid body.

Characteristics of carotid body chemosensitivity in NADPH oxidase-deficient mice

2002 ◽  
Vol 282 (1) ◽  
pp. C27-C33 ◽  
Author(s):  
L. He ◽  
J. Chen ◽  
B. Dinger ◽  
K. Sanders ◽  
K. Sundar ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Nadph Oxidase ◽  
Carotid Body ◽  
Gene Knockout ◽  
Type I ◽  
Type I Cells ◽  
Carotid Bodies ◽  
Marker Antigen ◽  
I Cells

Various heme-containing proteins have been proposed as primary molecular O2 sensors for hypoxia-sensitive type I cells in the mammalian carotid body. One set of data in particular supports the involvement of a cytochrome b NADPH oxidase that is commonly found in neutrophils. Subunits of this enzyme have been immunocytochemically localized in type I cells, and diphenyleneiodonium, an inhibitor of the oxidase, increases carotid body chemoreceptor activity. The present study evaluated immunocytochemical and functional properties of carotid bodies from normal mice and from mice with a disrupted gp91 phagocytic oxidase (gp91 phox ) DNA sequence gene knockout (KO), a gene that codes for a subunit of the neutrophilic form of NADPH oxidase. Immunostaining for tyrosine hydroxylase, a signature marker antigen for type I cells, was found in groups or lobules of cells displaying morphological features typical of the O2-sensitive cells in other species, and the incidence of tyrosine hydroxylase-immunopositive cells was similar in carotid bodies from both strains of mice. Studies of whole cell K+currents also revealed identical current-voltage relationships and current depression by hypoxia in type I cells dissociated from normal vs. KO animals. Likewise, hypoxia-evoked increases in intracellular Ca2+ concentration were not significantly different for normal and KO type I cells. The whole organ response to hypoxia was evaluated in recordings of carotid sinus nerve activity in vitro. In these experiments, responses elicited by hypoxia and by the classic chemoreceptor stimulant nicotine were also indistinguishable in normal vs. KO preparations. Our data demonstrate that carotid body function remains intact after sequence disruption of the gp91 phox gene. These findings are not in accord with the hypothesis that the phagocytic form of NADPH oxidase acts as a primary O2 sensor in arterial chemoreception.

scholarly journals Immunohistochemical Characteristics of the Human Carotid Body in the Antenatal and Postnatal Periods of Development

2021 ◽  
Vol 22 (15) ◽  
pp. 8222
Author(s):  
Dmitry Otlyga ◽  
Ekaterina Tsvetkova ◽  
Olga Junemann ◽  
Sergey Saveliev
Keyword(s):  
Tyrosine Hydroxylase ◽  
Carotid Body ◽  
Nerve Fibers ◽  
Individual Development ◽  
Endocrine Function ◽  
Type I ◽  
Type I Cells ◽  
Carotid Bodies ◽  
I Cells ◽  
Human Carotid

The evolutionary and ontogenetic development of the carotid body is still understudied. Research aimed at studying the comparative morphology of the organ at different periods in the individual development of various animal species should play a crucial role in understanding the physiology of the carotid body. However, despite more than two centuries of study, the human carotid body remains poorly understood. There are many knowledge gaps in particular related to the antenatal development of this structure. The aim of our work is to study the morphological and immunohistochemical characteristics of the human carotid body in the antenatal and postnatal periods of development. We investigated the human carotid bodies from 1 embryo, 20 fetuses and 13 adults of different ages using samples obtained at autopsy. Immunohistochemistry revealed expression of βIII-tubulin and tyrosine hydroxylase in the type I cells and nerve fibers at all periods of ontogenesis; synaptophysin and PGP9.5 in the type I cells in some of the antenatal cases and all of the postnatal cases; 200 kDa neurofilaments in nerve fibers in some of the antenatal cases and all of the postnatal cases; and GFAP and S100 in the type II cells and Schwann cells in some of the antenatal cases and all of the postnatal cases. A high level of tyrosine hydroxylase in the type I cells was a distinctive feature of the antenatal carotid bodies. On the contrary, in the type I cells of adults, the expression of tyrosine hydroxylase was significantly lower. Our data suggest that the human carotid body may perform an endocrine function in the antenatal period, while in the postnatal period of development, it loses this function and becomes a chemosensory organ.

Sign in / Sign up

Export Citation Format

Share Document