scholarly journals Gasotransmitter Regulation of Ion Channels: A Key Step in O2 Sensing By the Carotid Body

Physiology ◽  
2014 ◽  
Vol 29 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Nanduri R. Prabhakar ◽  
Chris Peers
Keyword(s):  
Ion Channels ◽  
Carotid Body ◽  
Physiological Responses ◽  
Current Understanding ◽  
Body Function ◽  
Arterial Blood ◽  
Carotid Bodies ◽  
Review Current ◽  
O2 Sensing

Carotid bodies detect hypoxia in arterial blood, translating this stimulus into physiological responses via the CNS. It is long established that ion channels are critical to this process. More recent evidence indicates that gasotransmitters exert powerful influences on O2 sensing by the carotid body. Here, we review current understanding of hypoxia-dependent production of gasotransmitters, how they regulate ion channels in the carotid body, and how this impacts carotid body function.

scholarly journals Hydroxycobalamin Reveals the Involvement of Hydrogen Sulfide in the Hypoxic Responses of Rat Carotid Body Chemoreceptor Cells

Antioxidants ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 62
Author(s):  
Teresa Gallego-Martin ◽  
Jesus Prieto-Lloret ◽  
Philip Aaronson ◽  
Asuncion Rocher ◽  
Ana Obeso
Keyword(s):  
Hydrogen Sulfide ◽  
Carotid Body ◽  
Oxygen Sensor ◽  
Catecholamine Release ◽  
Glomus Cells ◽  
Arterial Blood ◽  
Carotid Bodies ◽  
High K ◽  
Chemoreceptor Cells ◽  
Ca2 Channels

Carotid body (CB) chemoreceptor cells sense arterial blood PO2, generating a neurosecretory response proportional to the intensity of hypoxia. Hydrogen sulfide (H2S) is a physiological gaseous messenger that is proposed to act as an oxygen sensor in CBs, although this concept remains controversial. In the present study we have used the H2S scavenger and vitamin B12 analog hydroxycobalamin (Cbl) as a new tool to investigate the involvement of endogenous H2S in CB oxygen sensing. We observed that the slow-release sulfide donor GYY4137 elicited catecholamine release from isolated whole carotid bodies, and that Cbl prevented this response. Cbl also abolished the rise in [Ca2+]i evoked by 50 µM NaHS in enzymatically dispersed CB glomus cells. Moreover, Cbl markedly inhibited the catecholamine release and [Ca2+]i rise caused by hypoxia in isolated CBs and dispersed glomus cells, respectively, whereas it did not alter these responses when they were evoked by high [K+]e. The L-type Ca2+ channel blocker nifedipine slightly inhibited the rise in CB chemoreceptor cells [Ca2+]i elicited by sulfide, whilst causing a somewhat larger attenuation of the hypoxia-induced Ca2+ signal. We conclude that Cbl is a useful and specific tool for studying the function of H2S in cells. Based on its effects on the CB chemoreceptor cells we propose that endogenous H2S is an amplifier of the hypoxic transduction cascade which acts mainly by stimulating non-L-type Ca2+ channels.

Relative latency of responses of chemoreceptor afferents from aortic and carotid bodies

1980 ◽  
Vol 48 (2) ◽  
pp. 362-369 ◽  
Author(s):  
S. Lahiri ◽  
T. Nishino ◽  
E. Mulligan ◽  
A. Mokashi
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Carotid Body ◽  
Blood Gases ◽  
Unexpected Result ◽  
Blood Gas ◽  
Arterial Blood Gases ◽  
Carotid Chemoreceptors ◽  
Arterial Blood ◽  
Carotid Bodies

Discharges from aortic and carotid body chemoreceptor afferents were simultaneously recorded in 18 anesthetized cats to test the hypothesis that aortic chemoreceptors, because of their proximity to the heart, respond to changes in arterial blood gases before carotid chemoreceptors. We found that carotid chemoreceptor responses to the onset of hypoxia and hypercapnia, and to the intravenously administered excitatory drugs (cyanide, nicotine, and doxapram), preceded those of aortic chemoreceptors. Postulating that this unexpected result was due to differences in microcirculation and mass transport, we also investigated their relative speed of responses to changes in arterial blood pressure. The aortic chemoreceptors responded to decreases in arterial blood pressure before the carotid chemoreceptors, supporting the idea that the aortic body has microcirculatory impediments not generally present in the carotid body. These findings strengthened the concept that carotid bodies are more suited for monitoring blood gas changes due to respiration, whereas aortic bodies are for monitoring circulation.

Interplay among carotid sinus, cardiopulmonary, and carotid body reflexes in dogs

1976 ◽  
Vol 230 (1) ◽  
pp. 19-24 ◽  
Author(s):  
G Mancia ◽  
JT Shepherd ◽  
DE Donald
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Vascular Resistance ◽  
Carotid Body ◽  
Carotid Sinus ◽  
Dominant Role ◽  
Arterial Blood ◽  
Carotid Bodies ◽  
Sinus Pressure

Interactions among vascular reflexes evoked from carotid sinuses, carotid bodies, and cardiopulmonary region were examined in anesthetized, atropinized, and respired dogs with aortic nerves cut. The carotid sinuses were perfused at 220, 150, and 40-50 mmHg; the chemoreceptors were stimulated by perfusion with hypoxic hypercapnic blood. Cardiopulmonary vasomotor inhibition was interrupted by vagal cold block. Measurements were made of arterial blood pressure and of kidney and hindlimb vascular resistance. At sinus pressures less than 170-160 mmHg, cardiopulmonary vasomotor inhibition increased with increase in blood volume. At high sinus pressure, interruption of this augmented cardiopulmonary inhibition was as ineffective in changing vascular resistance as interruption of the lesser inhibition present during normovolemia. Chemoreceptor stimulation increased the response to vagal block at intermediate but not at high or low sinus pressure. The studies demonstrate the dominant role of the carotid sinus reflex when the three systems interact and the ineffectiveness of chemoreceptor stimulation when carotid or cardiopulmonary inhibition is maximal.

Effect of dopamine on hypoxic ventilatory response of sedated piglets with intact and denervated carotid bodies

1994 ◽  
Vol 77 (1) ◽  
pp. 285-289 ◽  
Author(s):  
C. Suguihara ◽  
D. Hehre ◽  
E. Bancalari
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Carotid Body ◽  
Minute Ventilation ◽  
Initial Increase ◽  
Dopamine Antagonist ◽  
Drug Infusion ◽  
Endogenous Dopamine ◽  
Arterial Blood ◽  
Carotid Bodies

To determine whether the neonatal hypoxic ventilatory depression is in part produced by an increased endogenous dopamine release that can depress the activity of central and peripheral chemoreceptors, 31 sedated and spontaneously breathing newborn piglets [age 5 +/- 1 (SD) days; weight 1.7 +/- 0.4 kg] were randomly assigned to an intact carotid body or a chemodenervated group. Minute ventilation (VE), arterial blood pressure, and cardiac output (CO) were measured in room air before infusion of saline or the dopamine antagonist flupentixol (0.2 mg/kg i.v.) and 15 min after drug infusion and were repeated after 10 min of hypoxia (inspiratory O2 fraction = 0.10). VE increased significantly after 10 min of hypoxia in the piglets that received flupentixol independent of whether the carotid bodies were intact or denervated. However, the increase in VE was largest and sustained throughout the 10 min of hypoxia only in the intact carotid body flupentixol group. As expected, the initial increase in VE with hypoxia was abolished by carotid body denervation. Changes in arterial blood gases, CO, and mean arterial blood pressure with hypoxia were not different among groups. These results demonstrate that flupentixol reverses the late hypoxic decrease in VE, acting through peripheral and central dopamine receptors. This effect is not related to changes in cardiovascular function or acid-base status.

scholarly journals Autonomic innervation of the carotid body as a determinant of its sensitivity: implications for cardiovascular physiology and pathology

2020 ◽  
Author(s):  
Fernanda Brognara ◽  
Igor S A Felippe ◽  
Helio C Salgado ◽  
Julian F R Paton
Keyword(s):  
Blood Flow ◽  
Carotid Body ◽  
Neural Control ◽  
Metabolic Diseases ◽  
Cell Activity ◽  
Autonomic Innervation ◽  
Autonomic Nerves ◽  
Parasympathetic Nerves ◽  
Arterial Blood ◽  
Carotid Bodies

Abstract The motivation for this review comes from the emerging complexity of the autonomic innervation of the carotid body (CB) and its putative role in regulating chemoreceptor sensitivity. With the carotid bodies as a potential therapeutic target for numerous cardiorespiratory and metabolic diseases, an understanding of the neural control of its circulation is most relevant. Since nerve fibres track blood vessels and receive autonomic innervation, we initiate our review by describing the origins of arterial feed to the CB and its unique vascular architecture and blood flow. Arterial feed(s) vary amongst species and, unequivocally, the arterial blood supply is relatively high to this organ. The vasculature appears to form separate circuits inside the CB with one having arterial venous anastomoses. Both sympathetic and parasympathetic nerves are present with postganglionic neurons located within the CB or close to it in the form of paraganglia. Their role in arterial vascular resistance control is described as is how CB blood flow relates to carotid sinus afferent activity. We discuss non-vascular targets of autonomic nerves, their possible role in controlling glomus cell activity, and how certain transmitters may relate to function. We propose that the autonomic nerves sub-serving the CB provide a rapid mechanism to tune the gain of peripheral chemoreflex sensitivity based on alterations in blood flow and oxygen delivery, and might provide future therapeutic targets. However, there remain a number of unknowns regarding these mechanisms that require further research that is discussed.

Control of diving responses by carotid bodies and baroreceptors in ducks

1982 ◽  
Vol 242 (1) ◽  
pp. R105-R108 ◽  
Author(s):  
R. S. Lillo ◽  
D. R. Jones
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Carotid Body ◽  
Cardiovascular Responses ◽  
Pekin Ducks ◽  
Cardiac Responses ◽  
Arterial Blood ◽  
Carotid Bodies ◽  
Carotid Body Chemoreceptors

The precise role of carotid body chemoreceptors and systemic baroreceptors in cardiovascular responses during experimental diving in ducks is controversial. The diving responses of chronically baroreceptor-denervated, chemoreceptor-denervated, and combined baroreceptor- and chemoreceptor-denervated White Pekin ducks, Anas platyrhynchos, were compared with those of intact and sham-operated birds. All three types of denervation elevated predive heart rates on average by 100-150 beats/min. During submergence, the cardiac rate of the barodenervates quickly dropped and after 60 s stabilized at levels similar to those of submerged intact ducks for the remainder of a 2-min dive. However, arterial blood pressure declined drastically in the barodenervates. Ducks without functional carotid bodies showed significant bradycardia during submergence, although heart rate only fell to the predive rate of intact animals. Birds with combined baroreceptor and chemoreceptor denervation exhibited the same degree of bradycardia as chemoreceptor denervates, and arterial blood pressure rose spectacularly during a dive. It is concluded that during experimental diving in ducks 1) cardiac responses are not baroreflexive in origin, 2) the major portion of bradycardia is due to stimulation of carotid body chemoreceptors, and 3) intact system baroreceptors appear essential for maintenance of blood pressure.

scholarly journals Recent advances in understanding the physiology of hypoxic sensing by the carotid body

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1900 ◽  
Author(s):  
Nanduri R. Prabhakar ◽  
Ying-Jie Peng ◽  
Jayasri Nanduri
Keyword(s):  
Carotid Body ◽  
Complex I ◽  
Nadh Dehydrogenase ◽  
Type I ◽  
The Past ◽  
Arterial Blood ◽  
A Subunit ◽  
Reflex Stimulation ◽  
I Cells ◽  
O2 Sensing

Hypoxia resulting from reduced oxygen (O2) levels in the arterial blood is sensed by the carotid body (CB) and triggers reflex stimulation of breathing and blood pressure to maintain homeostasis. Studies in the past five years provided novel insights into the roles of heme oxygenase-2 (HO-2), a carbon monoxide (CO)-producing enzyme, and NADH dehydrogenase Fe-S protein 2, a subunit of the mitochondrial complex I, in hypoxic sensing by the CB. HO-2 is expressed in type I cells, the primary O2-sensing cells of the CB, and binds to O2 with low affinity. O2-dependent CO production from HO-2 mediates hypoxic response of the CB by regulating H2S generation. Mice lacking NDUFS2 show that complex I-generated reactive oxygen species acting on K+ channels confer type I cell response to hypoxia. Whether these signaling pathways operate synergistically or independently remains to be studied.

scholarly journals CaV3.2 T-type Ca2+ channels in H2S-mediated hypoxic response of the carotid body

2015 ◽  
Vol 308 (2) ◽  
pp. C146-C154 ◽  
Author(s):  
Vladislav V. Makarenko ◽  
Ying-Jie Peng ◽  
Guoxiang Yuan ◽  
Aaron P. Fox ◽  
Ganesh K. Kumar ◽  
...  
Keyword(s):  
Carotid Body ◽  
Sensory Nerve ◽  
Wild Type ◽  
Glomus Cells ◽  
Arterial Blood ◽  
Carotid Bodies ◽  
Intracellular Ca ◽  
Ca2 Channels ◽  
Body Response

Arterial blood O2 levels are detected by specialized sensory organs called carotid bodies. Voltage-gated Ca2+ channels (VGCCs) are important for carotid body O2 sensing. Given that T-type VGCCs contribute to nociceptive sensation, we hypothesized that they participate in carotid body O2 sensing. The rat carotid body expresses high levels of mRNA encoding the α1H-subunit, and α1H protein is localized to glomus cells, the primary O2-sensing cells in the chemoreceptor tissue, suggesting that CaV3.2 is the major T-type VGCC isoform expressed in the carotid body. Mibefradil and TTA-A2, selective blockers of the T-type VGCC, markedly attenuated elevation of hypoxia-evoked intracellular Ca2+ concentration, secretion of catecholamines from glomus cells, and sensory excitation of the rat carotid body. Similar results were obtained in the carotid body and glomus cells from CaV3.2 knockout ( Cacna1h−/−) mice. Since cystathionine-γ-lyase (CSE)-derived H2S is a critical mediator of the carotid body response to hypoxia, the role of T-type VGCCs in H2S-mediated O2 sensing was examined. Like hypoxia, NaHS, a H2S donor, increased intracellular Ca2+ concentration and augmented carotid body sensory nerve activity in wild-type mice, and these effects were markedly attenuated in Cacna1h−/− mice. In wild-type mice, TTA-A2 markedly attenuated glomus cell and carotid body sensory nerve responses to hypoxia, and these effects were absent in CSE knockout mice. These results demonstrate that CaV3.2 T-type VGCCs contribute to the H2S-mediated carotid body response to hypoxia.

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.

Hypoventilation in ponies after carotid body denervation

1976 ◽  
Vol 40 (2) ◽  
pp. 184-190 ◽  
Author(s):  
G. E. Bisgard ◽  
H. V. Forster ◽  
J. A. Orr ◽  
D. D. Buss ◽  
C. A. Rawlings ◽  
...  
Keyword(s):  
Carotid Body ◽  
Blood Gases ◽  
Acid Base Balance ◽  
Arterial Blood ◽  
Carotid Bodies ◽  
Base Balance ◽  
Alveolar Hypoventilation ◽  
Unanesthetized Animals ◽  
Normal Ventilation ◽  
Carotid Body Denervation

Seven ponies were subjected to carotid body denervation (CD) and two ponies were sham operated (S). Measurement of arterial blood gases and arterial blood and cerebrospinal fluid (CSF) acid-base balance were made prior to and 1,2,4,9, and 17 wks after surgery in unanesthetized animals. Resting ventilation and ventilatory responsiveness to hypoxia and NaCN infusion were assessed prior to and 2,9, and 17 wks after surgery. Alveolar hypoventilation in the CD ponies was marked 1–2 wk after surgery when VE and VA were reduced 40% and 10%, respectively, from control and PaCO2 was 12–15 mmHg above control. However, the effect was not nearly as great 4, 9, and 17 wk after surgery when the PaCO2 stabilized at approximately 6 mmHg above control PaCO2. Arterial blood pH was normal in the hypercapnic CD ponies, but CSF pH remained acid relative to normal throughout the 17-wk period. Changes in ventilatory responsiveness to hypoxia and NaCN tended to parallel changes in resting ventilation. These findings suggest: 1) the carotid bodies are essential in ponies to maintain normal ventilation: 2) in CD ponies peripheral chemosensitivity is partially regained at some unestablished locus; and 3) pH compensating mechanisms in chronically hypercapnic ponies function relatively better in blood than in CSF.

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