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Constancio Gonzalez - One of the best experts on this subject based on the ideXlab platform.

  • Effects of low glucose on Carotid Body Chemoreceptor cell activity studied in cultures of intact organs and in dissociated cells.
    American Journal of Physiology-Cell Physiology, 2012
    Co-Authors: Teresa Gallego-martin, Ana Obeso, R. Rigual, Silvia Fernandez-martinez, Constancio Gonzalez
    Abstract:

    The participation of the Carotid Body (CB) in glucose homeostasis and evidence obtained in simplified cultured CB slices or dissociated cells have led to the proposal that CB Chemoreceptor cells ar...

  • some reflections on intermittent hypoxia does it constitute the translational niche for Carotid Body Chemoreceptor researchers
    Advances in Experimental Medicine and Biology, 2012
    Co-Authors: Constancio Gonzalez, R. Rigual, Ana Obeso, Asuncion Rocher, Teresa Agapito, Sara Yubero, Angela M Gomeznino, Jose M Montserrat
    Abstract:

    The views presented in this article are the fruit of reflections and discussion with my colleagues at Valladolid and with the members of the Sleep Apnea Hypopnea Syndrome Group of the CIBERES (Spain). We have assembled the article in three sections. In the first one we provide a mechanistic description of obstructive sleep apnea (OSA) and all of its components, including the repetitive episodes of upper airways (UA) obstruction and accompanying hypoxic hypoxia, the respiratory efforts to fight and overcome the obstruction, and the sleep fragmentation due to the hypoxia-triggered arousal reactions, all events occurring during sleep hours with frequencies that might reach up >40–50 episodes/sleep hour. When OSA is accompanied by some of the elements of a big cohort of associated pathologies (vascular, metabolic, and neuropsychiatric) it conforms the obstructive sleep apnea syndrome (OSAS). The high frequency of OSAS in adults (>35 years old) and the costs in every regard of the treatment makes the syndrome a primary importance socio-sanitary problem. In the second section, we describe the experimental models of OSAS, basically the episodic repetitive hypoxic model described by Fletcher and coworkers in 1992, today named in short intermittent hypoxia (IH). From these lines, we want to call for some kind of consensus among researchers to lessen the dispersion of IH protocols. Finally, in the last section we intend to share our optimism with all ISAC members. The optimism is based on the recognition that Carotid Body (CB) Chemoreceptors are critical elements of one of the main pathophysiologic loops in the genesis of OSAS. Therefore, we believe that all of us, as ISAC members, are well qualified to contribute in multidisciplinary research teams with well defined translational interests.

  • EPAC signalling pathways are involved in low PO2 chemoreception in Carotid Body Chemoreceptor cells.
    The Journal of physiology, 2009
    Co-Authors: Asuncion Rocher, Ana I Caceres, Laura Almaraz, Constancio Gonzalez
    Abstract:

    Chemoreceptor cells of the Carotid bodies (CB) are activated by hypoxia and acidosis, responding with an increase in their rate of neurotransmitter release, which in turn increases the electrical activity in the Carotid sinus nerve and evokes a homeostatic hyperventilation. Studies in isolated Chemoreceptor cells have shown that moderate hypoxias ( 46 mmHg) produces smaller depolarisations and comparable Ca(2+) transients but a much higher catecholamine (CA) release response in intact CBs than intense acidic/hypercapnic stimuli (20% CO(2), pH 6.6). Similarly, intense hypoxia ( 20 mmHg) produces smaller depolarizations and Ca(2+) transients in isolated Chemoreceptor cells but a higher CA release response in intact CBs than a pure depolarizing stimulus (30-35 mm external K(+)). Studying the mechanisms responsible for these differences we have found the following. (1) Acidic hypercapnia inhibited I(Ca) (60%; whole cell) and CA release (45%; intact CB) elicited by ionomycin and high K(+). (2) Adenylate cyclase inhibition (SQ-22536; 80 microm) inhibited the hypoxic release response (>50%) and did not affect acidic/hypercapnic release, evidencing that the high gain of hypoxia to elicit neurotransmitter release is cAMP dependent. (3) The last effect was independent of PKA activation, as three kinase inhibitors (H-89, KT 5720 and Rp-cAMP; 10 x IC(50)) did not alter the hypoxic release response. (4) The Epac (exchange protein activated by cAMP) activator (8-pCPT-2-O-Me-cAMP, 100 microm) reversed the effects of the cyclase inhibitor. (5) The Epac inhibitor brefeldin A (100 microm) inhibited (54%) hypoxic induced release. Our findings show for the first time that an Epac-mediated pathway mediates O(2) sensing/transduction in Chemoreceptor cells.

  • Effects of mitochondrial poisons on glutathione redox potential and Carotid Body Chemoreceptor activity
    Respiratory Physiology & Neurobiology, 2009
    Co-Authors: A. Gómez-niño, M. T. Agapito, Ana Obeso, Constancio Gonzalez
    Abstract:

    Abstract Low oxygen sensing in Chemoreceptor cells involves the inhibition of specific plasma membrane K + channels, suggesting that mitochondria-derived reactive oxygen species (ROS) link hypoxia to K + channel inhibition, subsequent cell depolarization and activation of neurotransmitter release. We have used several mitochondrial poisons, alone and in combination with the antioxidant N-acetylcysteine (NAC), and quantify their capacity to alter GSH/GSSG levels and glutathione redox potential ( E GSH ) in rat diaphragm. Selected concentrations of mitochondrial poisons with or without NAC were tested for their capacity to activate neurotransmitter release in Chemoreceptor cells and to alter ATP levels in intact rat Carotid Body (CB). We found that rotenone (1 μM), antimycin A (0.2 μg/ml) and sodium azide (5 mM) decreased E GSH ; NAC restored E GSH to control values. At those concentrations mitochondrial poisons activated neurotransmitter release from CB Chemoreceptor cells and decreased CB ATP levels, NAC being ineffective to modify these responses. Additional experiments with 3-nitroprionate (5 mM), lower concentrations of rotenone and dinitrophenol revealed variable relationships between E GSH and Chemoreceptor cell neurotransmitter release responses and ATP levels. These findings indicate a lack of correlation between mitochondrial-generated modifications of E GSH and Chemoreceptor cells activity. This lack of correlation renders unlikely that alteration of mitochondrial production of ROS is the physiological pathway Chemoreceptor cells use to signal hypoxia.

  • General redox environment and Carotid Body Chemoreceptor function.
    American Journal of Physiology-Cell Physiology, 2009
    Co-Authors: M. T. Agapito, Constancio Gonzalez, Gloria Sanz-alfayate, A. Gómez-niño, Ana Obeso
    Abstract:

    Carotid Body (CB) Chemoreceptor cells detect physiological levels of hypoxia and generate a hyperventilation, homeostatic in nature, aimed to minimize the deleterious effects of hypoxia. Intimate m...

Ana Obeso - One of the best experts on this subject based on the ideXlab platform.

  • Hydroxycobalamin Reveals the Involvement of Hydrogen Sulfide in the Hypoxic Responses of Rat Carotid Body Chemoreceptor Cells
    Antioxidants, 2019
    Co-Authors: Teresa Gallego-martin, Asuncion Rocher, Jesus Prieto-lloret, Philip I. Aaronson, Ana Obeso
    Abstract:

    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.

  • Guinea Pig Oxygen-Sensing and Carotid Body Functional Properties
    Frontiers Media S.A., 2017
    Co-Authors: Elvira Gonzalez-obeso, Ana Obeso, Elena Olea, Inmaculada Docio, Angel Cogolludo, Asuncion Rocher
    Abstract:

    Mammals have developed different mechanisms to maintain oxygen supply to cells in response to hypoxia. One of those mechanisms, the Carotid Body (CB) Chemoreceptors, is able to detect physiological hypoxia and generate homeostatic reflex responses, mainly ventilatory and cardiovascular. It has been reported that guinea pigs, originally from the Andes, have a reduced ventilatory response to hypoxia compared to other mammals, implying that CB are not completely functional, which has been related to genetically/epigenetically determined poor hypoxia-driven CB reflex. This study was performed to check the guinea pig CB response to hypoxia compared to the well-known rat hypoxic response. These experiments have explored ventilatory parameters breathing different gases mixtures, cardiovascular responses to acute hypoxia, in vitro CB response to hypoxia and other stimuli and isolated guinea pig Chemoreceptor cells properties. Our findings show that guinea pigs are hypotensive and have lower arterial pO2 than rats, probably related to a low sympathetic tone and high hemoglobin affinity. Those characteristics could represent a higher tolerance to hypoxic environment than other rodents. We also find that although CB are hypo-functional not showing chronic hypoxia sensitization, a small percentage of isolated Carotid Body Chemoreceptor cells contain tyrosine hydroxylase enzyme and voltage-dependent K+ currents and therefore can be depolarized. However hypoxia does not modify intracellular Ca2+ levels or catecholamine secretion. Guinea pigs are able to hyperventilate only in response to intense acute hypoxic stimulus, but hypercapnic response is similar to rats. Whether other brain areas are also activated by hypoxia in guinea pigs remains to be studied

  • Effects of low glucose on Carotid Body Chemoreceptor cell activity studied in cultures of intact organs and in dissociated cells.
    American Journal of Physiology-Cell Physiology, 2012
    Co-Authors: Teresa Gallego-martin, Ana Obeso, R. Rigual, Silvia Fernandez-martinez, Constancio Gonzalez
    Abstract:

    The participation of the Carotid Body (CB) in glucose homeostasis and evidence obtained in simplified cultured CB slices or dissociated cells have led to the proposal that CB Chemoreceptor cells ar...

  • some reflections on intermittent hypoxia does it constitute the translational niche for Carotid Body Chemoreceptor researchers
    Advances in Experimental Medicine and Biology, 2012
    Co-Authors: Constancio Gonzalez, R. Rigual, Ana Obeso, Asuncion Rocher, Teresa Agapito, Sara Yubero, Angela M Gomeznino, Jose M Montserrat
    Abstract:

    The views presented in this article are the fruit of reflections and discussion with my colleagues at Valladolid and with the members of the Sleep Apnea Hypopnea Syndrome Group of the CIBERES (Spain). We have assembled the article in three sections. In the first one we provide a mechanistic description of obstructive sleep apnea (OSA) and all of its components, including the repetitive episodes of upper airways (UA) obstruction and accompanying hypoxic hypoxia, the respiratory efforts to fight and overcome the obstruction, and the sleep fragmentation due to the hypoxia-triggered arousal reactions, all events occurring during sleep hours with frequencies that might reach up >40–50 episodes/sleep hour. When OSA is accompanied by some of the elements of a big cohort of associated pathologies (vascular, metabolic, and neuropsychiatric) it conforms the obstructive sleep apnea syndrome (OSAS). The high frequency of OSAS in adults (>35 years old) and the costs in every regard of the treatment makes the syndrome a primary importance socio-sanitary problem. In the second section, we describe the experimental models of OSAS, basically the episodic repetitive hypoxic model described by Fletcher and coworkers in 1992, today named in short intermittent hypoxia (IH). From these lines, we want to call for some kind of consensus among researchers to lessen the dispersion of IH protocols. Finally, in the last section we intend to share our optimism with all ISAC members. The optimism is based on the recognition that Carotid Body (CB) Chemoreceptors are critical elements of one of the main pathophysiologic loops in the genesis of OSAS. Therefore, we believe that all of us, as ISAC members, are well qualified to contribute in multidisciplinary research teams with well defined translational interests.

  • Effects of mitochondrial poisons on glutathione redox potential and Carotid Body Chemoreceptor activity
    Respiratory Physiology & Neurobiology, 2009
    Co-Authors: A. Gómez-niño, M. T. Agapito, Ana Obeso, Constancio Gonzalez
    Abstract:

    Abstract Low oxygen sensing in Chemoreceptor cells involves the inhibition of specific plasma membrane K + channels, suggesting that mitochondria-derived reactive oxygen species (ROS) link hypoxia to K + channel inhibition, subsequent cell depolarization and activation of neurotransmitter release. We have used several mitochondrial poisons, alone and in combination with the antioxidant N-acetylcysteine (NAC), and quantify their capacity to alter GSH/GSSG levels and glutathione redox potential ( E GSH ) in rat diaphragm. Selected concentrations of mitochondrial poisons with or without NAC were tested for their capacity to activate neurotransmitter release in Chemoreceptor cells and to alter ATP levels in intact rat Carotid Body (CB). We found that rotenone (1 μM), antimycin A (0.2 μg/ml) and sodium azide (5 mM) decreased E GSH ; NAC restored E GSH to control values. At those concentrations mitochondrial poisons activated neurotransmitter release from CB Chemoreceptor cells and decreased CB ATP levels, NAC being ineffective to modify these responses. Additional experiments with 3-nitroprionate (5 mM), lower concentrations of rotenone and dinitrophenol revealed variable relationships between E GSH and Chemoreceptor cell neurotransmitter release responses and ATP levels. These findings indicate a lack of correlation between mitochondrial-generated modifications of E GSH and Chemoreceptor cells activity. This lack of correlation renders unlikely that alteration of mitochondrial production of ROS is the physiological pathway Chemoreceptor cells use to signal hypoxia.

Asuncion Rocher - One of the best experts on this subject based on the ideXlab platform.

  • Hydroxycobalamin Reveals the Involvement of Hydrogen Sulfide in the Hypoxic Responses of Rat Carotid Body Chemoreceptor Cells
    Antioxidants, 2019
    Co-Authors: Teresa Gallego-martin, Asuncion Rocher, Jesus Prieto-lloret, Philip I. Aaronson, Ana Obeso
    Abstract:

    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.

  • Guinea Pig Oxygen-Sensing and Carotid Body Functional Properties
    Frontiers Media S.A., 2017
    Co-Authors: Elvira Gonzalez-obeso, Ana Obeso, Elena Olea, Inmaculada Docio, Angel Cogolludo, Asuncion Rocher
    Abstract:

    Mammals have developed different mechanisms to maintain oxygen supply to cells in response to hypoxia. One of those mechanisms, the Carotid Body (CB) Chemoreceptors, is able to detect physiological hypoxia and generate homeostatic reflex responses, mainly ventilatory and cardiovascular. It has been reported that guinea pigs, originally from the Andes, have a reduced ventilatory response to hypoxia compared to other mammals, implying that CB are not completely functional, which has been related to genetically/epigenetically determined poor hypoxia-driven CB reflex. This study was performed to check the guinea pig CB response to hypoxia compared to the well-known rat hypoxic response. These experiments have explored ventilatory parameters breathing different gases mixtures, cardiovascular responses to acute hypoxia, in vitro CB response to hypoxia and other stimuli and isolated guinea pig Chemoreceptor cells properties. Our findings show that guinea pigs are hypotensive and have lower arterial pO2 than rats, probably related to a low sympathetic tone and high hemoglobin affinity. Those characteristics could represent a higher tolerance to hypoxic environment than other rodents. We also find that although CB are hypo-functional not showing chronic hypoxia sensitization, a small percentage of isolated Carotid Body Chemoreceptor cells contain tyrosine hydroxylase enzyme and voltage-dependent K+ currents and therefore can be depolarized. However hypoxia does not modify intracellular Ca2+ levels or catecholamine secretion. Guinea pigs are able to hyperventilate only in response to intense acute hypoxic stimulus, but hypercapnic response is similar to rats. Whether other brain areas are also activated by hypoxia in guinea pigs remains to be studied

  • t type calcium channels in rat Carotid Body Chemoreceptor cells molecular and functional hallmarks
    2016
    Co-Authors: Inmaculada Docio, Ana Isabel Caceres, Elena Olea, Maria E Ramirez, Teresa Gallegomartin, Asuncion Rocher
    Abstract:

    Resumen del poster presentado al 14th International Meeting of the European Calcium Society, celebrado en Valladolid (Espana) del 25 al 29 de septiembre de 2016.

  • some reflections on intermittent hypoxia does it constitute the translational niche for Carotid Body Chemoreceptor researchers
    Advances in Experimental Medicine and Biology, 2012
    Co-Authors: Constancio Gonzalez, R. Rigual, Ana Obeso, Asuncion Rocher, Teresa Agapito, Sara Yubero, Angela M Gomeznino, Jose M Montserrat
    Abstract:

    The views presented in this article are the fruit of reflections and discussion with my colleagues at Valladolid and with the members of the Sleep Apnea Hypopnea Syndrome Group of the CIBERES (Spain). We have assembled the article in three sections. In the first one we provide a mechanistic description of obstructive sleep apnea (OSA) and all of its components, including the repetitive episodes of upper airways (UA) obstruction and accompanying hypoxic hypoxia, the respiratory efforts to fight and overcome the obstruction, and the sleep fragmentation due to the hypoxia-triggered arousal reactions, all events occurring during sleep hours with frequencies that might reach up >40–50 episodes/sleep hour. When OSA is accompanied by some of the elements of a big cohort of associated pathologies (vascular, metabolic, and neuropsychiatric) it conforms the obstructive sleep apnea syndrome (OSAS). The high frequency of OSAS in adults (>35 years old) and the costs in every regard of the treatment makes the syndrome a primary importance socio-sanitary problem. In the second section, we describe the experimental models of OSAS, basically the episodic repetitive hypoxic model described by Fletcher and coworkers in 1992, today named in short intermittent hypoxia (IH). From these lines, we want to call for some kind of consensus among researchers to lessen the dispersion of IH protocols. Finally, in the last section we intend to share our optimism with all ISAC members. The optimism is based on the recognition that Carotid Body (CB) Chemoreceptors are critical elements of one of the main pathophysiologic loops in the genesis of OSAS. Therefore, we believe that all of us, as ISAC members, are well qualified to contribute in multidisciplinary research teams with well defined translational interests.

  • EPAC signalling pathways are involved in low PO2 chemoreception in Carotid Body Chemoreceptor cells.
    The Journal of physiology, 2009
    Co-Authors: Asuncion Rocher, Ana I Caceres, Laura Almaraz, Constancio Gonzalez
    Abstract:

    Chemoreceptor cells of the Carotid bodies (CB) are activated by hypoxia and acidosis, responding with an increase in their rate of neurotransmitter release, which in turn increases the electrical activity in the Carotid sinus nerve and evokes a homeostatic hyperventilation. Studies in isolated Chemoreceptor cells have shown that moderate hypoxias ( 46 mmHg) produces smaller depolarisations and comparable Ca(2+) transients but a much higher catecholamine (CA) release response in intact CBs than intense acidic/hypercapnic stimuli (20% CO(2), pH 6.6). Similarly, intense hypoxia ( 20 mmHg) produces smaller depolarizations and Ca(2+) transients in isolated Chemoreceptor cells but a higher CA release response in intact CBs than a pure depolarizing stimulus (30-35 mm external K(+)). Studying the mechanisms responsible for these differences we have found the following. (1) Acidic hypercapnia inhibited I(Ca) (60%; whole cell) and CA release (45%; intact CB) elicited by ionomycin and high K(+). (2) Adenylate cyclase inhibition (SQ-22536; 80 microm) inhibited the hypoxic release response (>50%) and did not affect acidic/hypercapnic release, evidencing that the high gain of hypoxia to elicit neurotransmitter release is cAMP dependent. (3) The last effect was independent of PKA activation, as three kinase inhibitors (H-89, KT 5720 and Rp-cAMP; 10 x IC(50)) did not alter the hypoxic release response. (4) The Epac (exchange protein activated by cAMP) activator (8-pCPT-2-O-Me-cAMP, 100 microm) reversed the effects of the cyclase inhibitor. (5) The Epac inhibitor brefeldin A (100 microm) inhibited (54%) hypoxic induced release. Our findings show for the first time that an Epac-mediated pathway mediates O(2) sensing/transduction in Chemoreceptor cells.

S Fidone - One of the best experts on this subject based on the ideXlab platform.

  • enhanced nitric oxide mediated Chemoreceptor inhibition and altered cyclic gmp signaling in rat Carotid Body following chronic hypoxia
    American Journal of Physiology-lung Cellular and Molecular Physiology, 2007
    Co-Authors: J Chen, B Dinger, X Liu, S Fidone
    Abstract:

    Multiple studies have shown that chronic hypoxia (CH) elicits a time-dependent upregulation of Carotid Body Chemoreceptor sensitivity in mammals. In the present study, we demonstrate that enhanced excitation is accompanied by a parallel increase of nitric oxide (NO)-dependent inhibition, which acts via a CH-induced modification of the normal mechanism in O(2)-sensitive type I cells. The NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), elicits a progressively larger increase in Carotid sinus nerve (CSN) Chemoreceptor activity following incremental increases in CH exposure lasting 1-16 days. The inhibitory effect of the NO donor, S-nitroso-N-acetyl-penicillamine (SNAP), on CSN activity is enhanced following CH. However, the activation of soluble guanylate cyclase (sGC) by SNAP, assessed via production of cGMP, is impaired, along with decreased expression of sGC mRNA transcript. Inhibition of hypoxia-evoked Ca(2+) responses by SNAP is mediated via a cGMP/protein kinase G (PKG)-dependent mechanism in normal type I cells that is sensitive to the PKG inhibitor KT-5823, but following CH, inhibitory responses are minimally sensitive to PKG inhibition. The data are consistent with the hypothesis that CH hampers cGMP-mediated inhibition of type I cells in favor of an alternative mechanism.

  • effect of p47phox gene deletion on ros production and oxygen sensing in mouse Carotid Body Chemoreceptor cells
    American Journal of Physiology-lung Cellular and Molecular Physiology, 2005
    Co-Authors: B Dinger, Ana Obeso, S Fidone, Karl Sanders, John R Hoidal, L J Stensaas, C Gonzalez
    Abstract:

    Membrane potential in oxygen-sensitive type I cells in Carotid Body is controlled by diverse sets of voltage-dependent and -independent K+ channels. Coupling of Po2 to the open-closed state of chan...

  • Carotid Body Chemoreceptor activity in mice deficient in selected subunits of nadph oxidase
    Advances in Experimental Medicine and Biology, 2003
    Co-Authors: J Chen, B Dinger, Karl Sanders, Krishna M Sundar, John R Hoidal, S Fidone
    Abstract:

    Exposure of the Carotid Body to hypoxia elicits increased neural activity in the Carotid sinus nerve (CSN), and reflex cardio-pulmonary adjustments which mitigate the adverse effects of hypoxemia. Increased Carotid Body activity occurs at relatively moderate arterial P02, in contrast to the severe hypoxia required to elicit metabolic and functional adjustments in non-02 sensing tissues (S.J.Fidone et al. 1997). Chemosensory type I cells derived from neuroectoderm are responsible for this exquisite sensitivity, and numerous laboratories have reported that low P02 inhibits the conductance of a variety of voltage sensitive and voltage-insensitive K+-channels in these cells. Yet the molecular mechanism underlying the P02 modulation of cell currents remains uncertain and controversial (H.Acker et al 1994, A.M.Riesco-Fagundo et al2001). Various heme proteins have been proposed as primary O2 sensors, and one set of data in particular suggests the involvement of a multi-component cytochrome b-containing NADPH oxidase which may be similar if not identical to the superoxide generating enzyme commonly found in phagocytic cells (H.Acker et al. 1994) (H.Acker et al. 1994), but the relationship between PO2 and ROS levels in type I cells has not been firmly established. In other cells and tissues hypoxia can increase or decrease ROS production in either mitochondria or via NADPH oxidase (I.O’Kelly et al. 2000, G.B Waypa et al. 2001). In addition, the target of ROS in type I cells is an unknown and critical factor in determining the effect of NADPH oxidase on cell activity. Recent studies have indicated that voltage-sensitive K+-channels in type I cells are modulated by hypoxia via a mechanism independent of soluble factors such as ROS (A.M. Riesco-Fagundo et al. 2001). Thus ROS do not appear to be necessary for cell activation. On the other hand, if hypoxia enhances NADPH oxidase activity, elevated ROS levels may increase the open probability of K+-channels thus facilitating cell repolarization. Such a scheme is consistent with elevated CSN activity in p47phox-gene deleted animals. Clarification of these issues must await future measurements of the effect of hypoxia on NADPH oxidase activity, and evaluation of the interaction of ROS with the chemotransduction machinery in type I cells.

  • Evidence for two types of nicotinic receptors in the cat Carotid Body Chemoreceptor cells.
    Brain Research, 1997
    Co-Authors: Ana Obeso, L Almaraz, M A Gómez-niño, B Dinger, S Fidone, Constancio Gonzalez
    Abstract:

    Abstract Current concepts on the location and functional significance of nicotinic receptors in the Carotid Body rest on α -bungarotoxin binding and autoradiographic studies. Using an in vitro preparation of the cat Carotid Body whose catecholamine deposits have been labeled by prior incubation with the tritiated natural precursor [ 3 H]tyrosine, we have found that nicotine induces release of [ 3 H]catecholamines in a dose-dependent manner (IC 50 =9.81 μ M). We also found that mecamylamine (50 μ M) completely abolished the nicotine-induced release, while α -bungarotoxin (100 nM; ≈20 times its binding K d ) only reduced the release by 56%. These findings indicate that Chemoreceptor cells, and perhaps other Carotid Body structures, contain nicotinic receptors that are not sensitive to α -bungarotoxin and force a revision of the current concepts on cholinergic mechanisms in the Carotid Body chemoreception.

R. Rigual - One of the best experts on this subject based on the ideXlab platform.

  • Effects of low glucose on Carotid Body Chemoreceptor cell activity studied in cultures of intact organs and in dissociated cells.
    American Journal of Physiology-Cell Physiology, 2012
    Co-Authors: Teresa Gallego-martin, Ana Obeso, R. Rigual, Silvia Fernandez-martinez, Constancio Gonzalez
    Abstract:

    The participation of the Carotid Body (CB) in glucose homeostasis and evidence obtained in simplified cultured CB slices or dissociated cells have led to the proposal that CB Chemoreceptor cells ar...

  • some reflections on intermittent hypoxia does it constitute the translational niche for Carotid Body Chemoreceptor researchers
    Advances in Experimental Medicine and Biology, 2012
    Co-Authors: Constancio Gonzalez, R. Rigual, Ana Obeso, Asuncion Rocher, Teresa Agapito, Sara Yubero, Angela M Gomeznino, Jose M Montserrat
    Abstract:

    The views presented in this article are the fruit of reflections and discussion with my colleagues at Valladolid and with the members of the Sleep Apnea Hypopnea Syndrome Group of the CIBERES (Spain). We have assembled the article in three sections. In the first one we provide a mechanistic description of obstructive sleep apnea (OSA) and all of its components, including the repetitive episodes of upper airways (UA) obstruction and accompanying hypoxic hypoxia, the respiratory efforts to fight and overcome the obstruction, and the sleep fragmentation due to the hypoxia-triggered arousal reactions, all events occurring during sleep hours with frequencies that might reach up >40–50 episodes/sleep hour. When OSA is accompanied by some of the elements of a big cohort of associated pathologies (vascular, metabolic, and neuropsychiatric) it conforms the obstructive sleep apnea syndrome (OSAS). The high frequency of OSAS in adults (>35 years old) and the costs in every regard of the treatment makes the syndrome a primary importance socio-sanitary problem. In the second section, we describe the experimental models of OSAS, basically the episodic repetitive hypoxic model described by Fletcher and coworkers in 1992, today named in short intermittent hypoxia (IH). From these lines, we want to call for some kind of consensus among researchers to lessen the dispersion of IH protocols. Finally, in the last section we intend to share our optimism with all ISAC members. The optimism is based on the recognition that Carotid Body (CB) Chemoreceptors are critical elements of one of the main pathophysiologic loops in the genesis of OSAS. Therefore, we believe that all of us, as ISAC members, are well qualified to contribute in multidisciplinary research teams with well defined translational interests.

  • Role of voltage-dependent calcium channels in stimulus-secretion coupling in rabbit Carotid Body Chemoreceptor cells.
    The Journal of Physiology, 2005
    Co-Authors: Asuncion Rocher, Constancio Gonzalez, R. Rigual, Emilio Geijo-barrientos, Ana Isabel Caceres, Laura Almaraz
    Abstract:

    We have defined Ca2+ channel subtypes expressed in rabbit Carotid Body (CB) Chemoreceptor cells and their participation in the stimulus-evoked catecholamine (CA) release. Ca2+ currents (ICa) activated at –30 mV, peaked at +10 mV and were fully blocked by 200 μm Cd2+. L-type channels (sensitive to 2 μm nisoldipine) activated at –30 mV and carried 21 ± 2% of total ICa. Non-L-type channels activated at potentials positive to –10 mV and carried: N channels (sensitive to 1 μmω-conotoxin-GVIA) 16 ± 1% of total ICa, P/Q channels (sensitive to 3 μmω-conotoxin-MVIIC after nisoldipine plus GVIA) 23 ± 3% of total ICa and R channels (resistant to all blockers combined) 40 ± 3% of total ICa. CA release induced by hypoxia, hypercapnic acidosis, dinitrophenol (DNP) and high K+o in the intact CB was inhibited by 79–98% by 200 μm Cd2+. Hypoxia, hypercapnic acidosis and DNP, depolarized Chemoreceptor cells and eventually generated repetitive action potential discharge. Nisoldipine plus MVIIC nearly abolished the release of CAs induced by hypoxia and hypercapnic acidosis and reduced by 74% that induced by DNP. All these secretory responses were insensitive to GVIA. 30 and 100 mm K+o brought resting membrane potential (Em) of Chemoreceptor cells (–48.1 ± 1.2 mV) to –22.5 and +7.2 mV, respectively. Thirty millimolar K+o-evoked release was abolished by nisoldipine but that induced by 100 mm K+o was mediated by activation of L, N, and P/Q channels. Data show that tested stimuli depolarize rabbit CB Chemoreceptor cells and elicit CA release through Ca2+ entry via voltage-activated channels. Only L and P/Q channels are tightly coupled to the secretion of CA.

  • Role of voltage-dependent calcium channels in stimulus-secretion coupling in rabbit Carotid Body Chemoreceptor cells.
    The Journal of physiology, 2004
    Co-Authors: Asuncion Rocher, Constancio Gonzalez, R. Rigual, Emilio Geijo-barrientos, Ana Isabel Caceres, Laura Almaraz
    Abstract:

    We have defined Ca2+ channel subtypes expressed in rabbit Carotid Body (CB) Chemoreceptor cells and their participation in the stimulus-evoked catecholamine (CA) release. Ca2+ currents (I(Ca)) activated at -30 mV, peaked at +10 mV and were fully blocked by 200 microm Cd2+. L-type channels (sensitive to 2 microm nisoldipine) activated at -30 mV and carried 21 +/- 2% of total I(Ca). Non-L-type channels activated at potentials positive to -10 mV and carried: N channels (sensitive to 1 microM omega-conotoxin-GVIA) 16 +/- 1% of total I(Ca), P/Q channels (sensitive to 3 microM omega-conotoxin-MVIIC after nisoldipine plus GVIA) 23 +/- 3% of total I(Ca) and R channels (resistant to all blockers combined) 40 +/- 3% of total I(Ca). CA release induced by hypoxia, hypercapnic acidosis, dinitrophenol (DNP) and high K(+)(o) in the intact CB was inhibited by 79-98% by 200 microm Cd2+. Hypoxia, hypercapnic acidosis and DNP, depolarized Chemoreceptor cells and eventually generated repetitive action potential discharge. Nisoldipine plus MVIIC nearly abolished the release of CAs induced by hypoxia and hypercapnic acidosis and reduced by 74% that induced by DNP. All these secretory responses were insensitive to GVIA. 30 and 100 mm K(+)(o) brought resting membrane potential (E(m)) of Chemoreceptor cells (-48.1 +/- 1.2 mV) to -22.5 and +7.2 mV, respectively. Thirty millimolar K(+)(o)-evoked release was abolished by nisoldipine but that induced by 100 mm K(+)(o) was mediated by activation of L, N, and P/Q channels. Data show that tested stimuli depolarize rabbit CB Chemoreceptor cells and elicit CA release through Ca2+ entry via voltage-activated channels. Only L and P/Q channels are tightly coupled to the secretion of CA.

  • Effects of perinatal hyperoxia on Carotid Body Chemoreceptor activity in vitro.
    Advances in Experimental Medicine and Biology, 2003
    Co-Authors: Jesus Prieto-lloret, R. Rigual, Ana Obeso, José R. López-lópez, Asuncion Rocher, Ana Isabel Caceres, R. Bustamante, J. Castañeda, T. Perez-garcia, Teresa Agapito
    Abstract:

    The arterial Carotid Body (CB) Chemoreceptors are highly vascularized sensory organs located in the proximity of the Carotid artery bifurcation and formed by clusters of parenchymal cells. The cell clusters are penetrated by sensory fibers of the Carotid sinus nerve (CSN) which form synapses with the parenchymal Chemoreceptor cells. Functionally, the CBs are the origin of a regulatory loop devoted to restore O2 availability in situations of hypoxia (Richalet, 1997). To achieve this function Chemoreceptor cells detect blood PO2, being activated by hypoxia. Hypoxia increases the rate of the release of neurotransmitters from the cells augmenting the action potential frequency in the CSN; this increased activity stimulates the brainstem regulators of respiration and hyperventilation and increased arterial blood PO2 ensue (Gonzalez et al., 1994).