The Experts below are selected from a list of 81 Experts worldwide ranked by ideXlab platform
Colin A Nurse - One of the best experts on this subject based on the ideXlab platform.
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expanding role of atp as a versatile messenger at carotid and Aortic Body chemoreceptors
The Journal of Physiology, 2013Co-Authors: Nikol A Piskuric, Colin A NurseAbstract:Abstract In mammals, peripheral arterial chemoreceptors monitor blood chemicals (e.g. O2, CO2, H+, glucose) and maintain homeostasis via initiation of respiratory and cardiovascular reflexes. Whereas chemoreceptors in the carotid bodies (CBs), located bilaterally at the carotid bifurcation, control primarily respiratory functions, those in the more diffusely distributed Aortic bodies (ABs) are thought to regulate mainly cardiovascular functions. Functionally, CBs sense partial pressure of O2 (), whereas ABs are considered sensors of O2 content. How these organs, with essentially a similar complement of chemoreceptor cells, differentially process these two different types of signals remains enigmatic. Here, we review evidence that implicates ATP as a central mediator during information processing in the CB. Recent data allow an integrative view concerning its interactions at purinergic P2X and P2Y receptors within the chemosensory complex that contains elements of a ‘quadripartite synapse’. We also discuss recent studies on the cellular physiology of ABs located near the Aortic arch, as well as immunohistochemical evidence suggesting the presence of pathways for P2X receptor signalling. Finally, we present a hypothetical ‘quadripartite model’ to explain how ATP, released from red blood cells during hypoxia, could contribute to the ability of ABs to sense O2 content.
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Effects of chemostimuli on [Ca2+]i responses of rat Aortic Body type I cells and endogenous local neurons: comparison with carotid Body cells
The Journal of physiology, 2012Co-Authors: Nikol A Piskuric, Colin A NurseAbstract:Mammalian Aortic bodies (ABs) are putative peripheral arterial chemoreceptors whose function remains controversial, partly because information on their cellular physiology is lacking. In this study, we used ratiometric Ca2+ imaging to investigate for the first time chemosensitivity in short-term cultures of dissociated cells of juvenile rat ABs, located near the junction of the left vagus and recurrent laryngeal nerves. Among the surviving cell population were glomus or type I cell clusters, endogenous local neurons and glia-like cells. A variety of chemostimuli, including hypoxia, isohydric or acidic hypercapnia, and isocapnic acidosis, caused a rise in intracellular [Ca2+] in AB type I cells. The Δ[Ca2+]i responses were indistinguishable from those in carotid Body (CB) type I cells grown in parallel cultures from the same animals, and responses to acidic hypercapnia were prevented by the non-specific voltage-gated Ca2+ channel antagonist, 2 mm Ni2+. Furthermore, we identified a subpopulation (∼40%) of glia-like cells in AB cultures that resembled CB type II cells based on their approximately equal sensitivity to ATP and UTP, consistent with the expression of purinergic P2Y2 receptors. Finally, we showed that some local neurons, known to be uniquely associated with these AB paraganglia in situ, generated robust Δ[Ca2+]i responses to these chemostimuli. Thus, these AB type I cells and associated putative type II cells resemble those from the well-studied CB. Unlike the CB, however, they also associate with a special group of endogenous neurons which we propose may subserve a sensory function in local cardiovascular reflexes.
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confocal immunofluorescence study of rat Aortic Body chemoreceptors and associated neurons in situ and in vitro
The Journal of Comparative Neurology, 2011Co-Authors: Nikol A Piskuric, Cathy Vollmer, Colin A NurseAbstract:Aortic bodies (ABs) are putative peripheral arterial chemoreceptors, distributed near the Aortic arch. Though presumed to be analogous to the well-studied carotid bodies (CBs), their anatomical organization, innervation, and function are poorly understood. By using multilabel confocal immunofluorescence, we investigated the cellular organization, innervation, and neurochemistry of ABs in whole mounts of juvenile rat vagus and recurrent laryngeal (V-RL) nerves and in dissociated cell culture. Clusters of tyrosine hydroxylase-immunoreactive (TH-IR) glomus cells were routinely identified within these nerves. Unlike the CB, many neuronal cell bodies and processes, identified by peripherin (PR) and neurofilament/growth-associated protein (NF70/GAP-43) immunoreactivity, were closely associated with AB glomus clusters, especially near the V-RL bifurcation. Some neuronal cell bodies were immunopositive for P2X2 and P2X3 purinoceptor subunits, which were also found in nerve terminals surrounding glomus cells. Immunoreactivity against the vesicular acetylcholine transporter (VAChT) was detected in local neurons, glomus cells, and apposed nerve terminals. Few neurons were immunopositive for TH or neuronal nitric oxide synthase. A similar pattern of purinoceptor immunoreactivity was observed in tissue sections of adult rat V-RL nerves, except that glomus cells were weakly P2X3-IR. Dissociated monolayer cultures of juvenile rat V-RL nerves yielded TH-IR glomus clusters in intimate association with PR- or NF70/GAP-43-IR neurons and their processes, and glial fibrillary acidic protein-IR type II (sustentacular) cells. Cocultures survived for several days, wherein neurons expressed voltage-activated ionic currents and generated action potentials. Thus, this coculture model is attractive for investigating the role of glomus cells and local neurons in AB function.
Nikol A Piskuric - One of the best experts on this subject based on the ideXlab platform.
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expanding role of atp as a versatile messenger at carotid and Aortic Body chemoreceptors
The Journal of Physiology, 2013Co-Authors: Nikol A Piskuric, Colin A NurseAbstract:Abstract In mammals, peripheral arterial chemoreceptors monitor blood chemicals (e.g. O2, CO2, H+, glucose) and maintain homeostasis via initiation of respiratory and cardiovascular reflexes. Whereas chemoreceptors in the carotid bodies (CBs), located bilaterally at the carotid bifurcation, control primarily respiratory functions, those in the more diffusely distributed Aortic bodies (ABs) are thought to regulate mainly cardiovascular functions. Functionally, CBs sense partial pressure of O2 (), whereas ABs are considered sensors of O2 content. How these organs, with essentially a similar complement of chemoreceptor cells, differentially process these two different types of signals remains enigmatic. Here, we review evidence that implicates ATP as a central mediator during information processing in the CB. Recent data allow an integrative view concerning its interactions at purinergic P2X and P2Y receptors within the chemosensory complex that contains elements of a ‘quadripartite synapse’. We also discuss recent studies on the cellular physiology of ABs located near the Aortic arch, as well as immunohistochemical evidence suggesting the presence of pathways for P2X receptor signalling. Finally, we present a hypothetical ‘quadripartite model’ to explain how ATP, released from red blood cells during hypoxia, could contribute to the ability of ABs to sense O2 content.
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Effects of chemostimuli on [Ca2+]i responses of rat Aortic Body type I cells and endogenous local neurons: comparison with carotid Body cells
The Journal of physiology, 2012Co-Authors: Nikol A Piskuric, Colin A NurseAbstract:Mammalian Aortic bodies (ABs) are putative peripheral arterial chemoreceptors whose function remains controversial, partly because information on their cellular physiology is lacking. In this study, we used ratiometric Ca2+ imaging to investigate for the first time chemosensitivity in short-term cultures of dissociated cells of juvenile rat ABs, located near the junction of the left vagus and recurrent laryngeal nerves. Among the surviving cell population were glomus or type I cell clusters, endogenous local neurons and glia-like cells. A variety of chemostimuli, including hypoxia, isohydric or acidic hypercapnia, and isocapnic acidosis, caused a rise in intracellular [Ca2+] in AB type I cells. The Δ[Ca2+]i responses were indistinguishable from those in carotid Body (CB) type I cells grown in parallel cultures from the same animals, and responses to acidic hypercapnia were prevented by the non-specific voltage-gated Ca2+ channel antagonist, 2 mm Ni2+. Furthermore, we identified a subpopulation (∼40%) of glia-like cells in AB cultures that resembled CB type II cells based on their approximately equal sensitivity to ATP and UTP, consistent with the expression of purinergic P2Y2 receptors. Finally, we showed that some local neurons, known to be uniquely associated with these AB paraganglia in situ, generated robust Δ[Ca2+]i responses to these chemostimuli. Thus, these AB type I cells and associated putative type II cells resemble those from the well-studied CB. Unlike the CB, however, they also associate with a special group of endogenous neurons which we propose may subserve a sensory function in local cardiovascular reflexes.
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confocal immunofluorescence study of rat Aortic Body chemoreceptors and associated neurons in situ and in vitro
The Journal of Comparative Neurology, 2011Co-Authors: Nikol A Piskuric, Cathy Vollmer, Colin A NurseAbstract:Aortic bodies (ABs) are putative peripheral arterial chemoreceptors, distributed near the Aortic arch. Though presumed to be analogous to the well-studied carotid bodies (CBs), their anatomical organization, innervation, and function are poorly understood. By using multilabel confocal immunofluorescence, we investigated the cellular organization, innervation, and neurochemistry of ABs in whole mounts of juvenile rat vagus and recurrent laryngeal (V-RL) nerves and in dissociated cell culture. Clusters of tyrosine hydroxylase-immunoreactive (TH-IR) glomus cells were routinely identified within these nerves. Unlike the CB, many neuronal cell bodies and processes, identified by peripherin (PR) and neurofilament/growth-associated protein (NF70/GAP-43) immunoreactivity, were closely associated with AB glomus clusters, especially near the V-RL bifurcation. Some neuronal cell bodies were immunopositive for P2X2 and P2X3 purinoceptor subunits, which were also found in nerve terminals surrounding glomus cells. Immunoreactivity against the vesicular acetylcholine transporter (VAChT) was detected in local neurons, glomus cells, and apposed nerve terminals. Few neurons were immunopositive for TH or neuronal nitric oxide synthase. A similar pattern of purinoceptor immunoreactivity was observed in tissue sections of adult rat V-RL nerves, except that glomus cells were weakly P2X3-IR. Dissociated monolayer cultures of juvenile rat V-RL nerves yielded TH-IR glomus clusters in intimate association with PR- or NF70/GAP-43-IR neurons and their processes, and glial fibrillary acidic protein-IR type II (sustentacular) cells. Cocultures survived for several days, wherein neurons expressed voltage-activated ionic currents and generated action potentials. Thus, this coculture model is attractive for investigating the role of glomus cells and local neurons in AB function.
Yoshikazu Nakazato - One of the best experts on this subject based on the ideXlab platform.
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Characteristics of 5-HT-containing chemoreceptor cells of the chicken Aortic Body.
The Journal of Physiology, 1999Co-Authors: Shigeo Ito, Toshio Ohta, Yoshikazu NakazatoAbstract:Voltage-dependent and oxygen-sensitive currents in 5-HT-containing epithelioid cells isolated from chicken thoracic aorta were examined using the whole-cell patch clamp technique. 5-HT immunoreactive cells were identified with Neutral Red. The release of 5-HT from chicken thoracic aorta in the presence of excess KCl and veratridine was also examined using HPLC. At a holding potential of −70 mV with CsCl pipette solution, depolarizing steps between −30 and +60 mV produced inward currents that were blocked by tetrodotoxin (0.2 μm). In the presence of tetrodotoxin and BaCl2 (5 mm), depolarizing steps evoked slow inward currents that were sensitive to CoCl2 (2 mm). Nifedipine (1 μm) decreased the currents to 79.4 ± 1.7%, and ω-conotoxin GVIA (1 μm) to 20.2 ± 3.8%. When KCl pipette solution was used, depolarizing potentials positive to −40 mV caused outward currents that were inhibited by tetraethylammonium chloride. The K+ currents evoked by depolarizing steps to +20 mV were reduced to 90.3 ± 0.8% by hypoxia in five out of seven cells. Two cells failed to respond to hypoxia. The K+ current response was partly decreased by Neutral Red (20 μm). Excess KCl (60 mm) and veratridine (30 μm) both caused the release of 5-HT from Aortic strips. 5-HT outputs induced by both stimuli were partly inhibited by nifedipine (1 μm) and by ω-conotoxin GVIA (1 μm), and were abolished by these drugs in combination and by extracellular Ca2+ removal. These results suggest that epithelioid cells containing 5-HT act as chemoreceptor cells in the chicken Aortic Body, having voltage-dependent Na+, K+, and L- and N-type Ca2+ channels, and oxygen-sensitive K+ channels. It is well known that there are two main chemoreceptor organs in the peripheral tissue, the carotid Body located in the carotid bifurcation and the Aortic Body located in the wall of the aorta. Evidence suggests that chemoreceptor cells in the carotid Body, type I cells, sense changes in plasma PO2, PCO2 and pH and then release transmitters which activate the sensory nerve endings of the carotid sinus nerve. Catecholamines such as dopamine and/or noradrenaline in the type I cells may act as transmitters to the sensory nerve endings (see review by Gonzalez et al. 1994). The carotid bodies of the rat, cat and human have been shown to contain not only catecholamines but also biogenic indoleamine, 5-HT (Chiocchio et al. 1967; Hellstrom, 1977; Perrin et al. 1986; Wang et al. 1992). Neuroendocrine cells of the airway neuroepithelial bodies, considered to be airway chemoreceptors, contain 5-HT but not dopamine (Cutz et al. 1993). In chicken carotid bodies, 5-HT has been reported to be dominant (Pearce et al. 1973; Yamamoto et al. 1989; Kameda, 1990). The release of dopamine from rabbit carotid bodies in response to hypoxia or excess KCl has been shown to be dependent on extracellular Ca2+ (Gonzalez et al. 1992), and chemoreceptor cells of the rabbit carotid Body are excitable cells with voltage-dependent Na+, K+ and Ca2+ channels (Duchen et al. 1988; Lopez-Barneo et al. 1988). Similar voltage-dependent channels are also seen in the neuroendocrine cells of the airway neuroepithelial bodies (Youngson et al. 1993). The mechanisms by which the type I cells of the carotid Body respond to changes in PO2 remain uncertain. In type I cells, a voltage-activated K+ current has been proposed to be inhibited by hypoxia (oxygen-sensitive K+ current) (Lopez-Barneo et al. 1988; Delpiano & Hescheler, 1989; Peers, 1990a). A similar oxygen-sensitive K+ current has been found in the neuroendocrine cells of the airway neuroepithelial bodies (Youngson et al. 1993), neonatal adrenal chromaffin cells (Thompson et al. 1997) and PC12 cells (Conforti & Millhorn, 1997). Quite recently, however, a novel oxygen-sensitive K+ current was reported in rat carotid Body type I cells, in which hypoxia inhibited voltage-insensitive resting K+ conductance (Buckler, 1997). Epithelioid cells containing 5-HT are aggregated into clusters and form a band of about 1 mm in width in the wall of the chicken thoracic aorta (Miyoshi et al. 1995). We have suggested that these cells are arterial chemoreceptors corresponding to the mammalian Aortic Body because hypoxic stimulation causes the release of 5-HT from pieces of chicken thoracic aorta (Ito et al. 1997). In comparison with the knowledge of properties of carotid chemoreceptor cells, less is known about the characteristics of chemoreceptor cells in the Aortic Body. Leech neurons containing catecholamines or 5-HT have been shown to be stained with a vital dye, Neutral Red (Stuart et al. 1974). Using this dye, it is possible that epithelioid cells containing 5-HT could be identified after dissociation from the chicken thoracic aorta. In the present experiments, we firstly examined whether or not Neutral Red-positive cells isolated from the chicken thoracic aorta contained 5-HT, and then examined the types of voltage-activated channels and oxygen-sensitive channels in Neutral Red-positive epithelioid cells using the whole-cell patch clamp technique. We also investigated characteristics of 5-HT secretion evoked by veratridine and excess KCl from pieces of chicken thoracic aorta.
Edward J Zuperku - One of the best experts on this subject based on the ideXlab platform.
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respiratory responses to Aortic and carotid chemoreceptor activation in the dog
Journal of Applied Physiology, 1991Co-Authors: Francis A Hopp, J L Seagard, Jurica Bajic, Edward J ZuperkuAbstract:Respiratory responses arising from both chemical stimulation of vascularly isolated Aortic Body (AB) and carotid Body (CB) chemoreceptors and electrical stimulation of Aortic nerve (AN) and carotid sinus nerve (CSN) afferents were compared in the anesthetized dog. Respiratory reflexes were measured as changes in inspiratory duration (TI), expiratory duration (TE), and peak averaged phrenic nerve activity (PPNG). Tonic AN and AB stimulations shortened TI and TE with no change in PPNG, while tonic CSN and CB stimulations shortened TE, increased PPNG, and transiently lengthened TI. Phasic AB and AN stimulations throughout inspiration shortened TI with no changes in PPNG or the following TE; however, similar phasic stimulations of the CB and CSN increased both TI and PPNG and decreased the following TE. Phasic AN stimulation during expiration decreased TE and the following TI with no change in PPNG. Similar stimulations of the CB and CSN decreased TE; however, the following TI and PPNG were increased. These findings differ from those found in the cat and suggest that Aortic chemoreceptors affect mainly phase timing, while carotid chemoreceptors affect both timing and respiratory drive.
Shigeo Ito - One of the best experts on this subject based on the ideXlab platform.
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Characteristics of 5-HT-containing chemoreceptor cells of the chicken Aortic Body.
The Journal of Physiology, 1999Co-Authors: Shigeo Ito, Toshio Ohta, Yoshikazu NakazatoAbstract:Voltage-dependent and oxygen-sensitive currents in 5-HT-containing epithelioid cells isolated from chicken thoracic aorta were examined using the whole-cell patch clamp technique. 5-HT immunoreactive cells were identified with Neutral Red. The release of 5-HT from chicken thoracic aorta in the presence of excess KCl and veratridine was also examined using HPLC. At a holding potential of −70 mV with CsCl pipette solution, depolarizing steps between −30 and +60 mV produced inward currents that were blocked by tetrodotoxin (0.2 μm). In the presence of tetrodotoxin and BaCl2 (5 mm), depolarizing steps evoked slow inward currents that were sensitive to CoCl2 (2 mm). Nifedipine (1 μm) decreased the currents to 79.4 ± 1.7%, and ω-conotoxin GVIA (1 μm) to 20.2 ± 3.8%. When KCl pipette solution was used, depolarizing potentials positive to −40 mV caused outward currents that were inhibited by tetraethylammonium chloride. The K+ currents evoked by depolarizing steps to +20 mV were reduced to 90.3 ± 0.8% by hypoxia in five out of seven cells. Two cells failed to respond to hypoxia. The K+ current response was partly decreased by Neutral Red (20 μm). Excess KCl (60 mm) and veratridine (30 μm) both caused the release of 5-HT from Aortic strips. 5-HT outputs induced by both stimuli were partly inhibited by nifedipine (1 μm) and by ω-conotoxin GVIA (1 μm), and were abolished by these drugs in combination and by extracellular Ca2+ removal. These results suggest that epithelioid cells containing 5-HT act as chemoreceptor cells in the chicken Aortic Body, having voltage-dependent Na+, K+, and L- and N-type Ca2+ channels, and oxygen-sensitive K+ channels. It is well known that there are two main chemoreceptor organs in the peripheral tissue, the carotid Body located in the carotid bifurcation and the Aortic Body located in the wall of the aorta. Evidence suggests that chemoreceptor cells in the carotid Body, type I cells, sense changes in plasma PO2, PCO2 and pH and then release transmitters which activate the sensory nerve endings of the carotid sinus nerve. Catecholamines such as dopamine and/or noradrenaline in the type I cells may act as transmitters to the sensory nerve endings (see review by Gonzalez et al. 1994). The carotid bodies of the rat, cat and human have been shown to contain not only catecholamines but also biogenic indoleamine, 5-HT (Chiocchio et al. 1967; Hellstrom, 1977; Perrin et al. 1986; Wang et al. 1992). Neuroendocrine cells of the airway neuroepithelial bodies, considered to be airway chemoreceptors, contain 5-HT but not dopamine (Cutz et al. 1993). In chicken carotid bodies, 5-HT has been reported to be dominant (Pearce et al. 1973; Yamamoto et al. 1989; Kameda, 1990). The release of dopamine from rabbit carotid bodies in response to hypoxia or excess KCl has been shown to be dependent on extracellular Ca2+ (Gonzalez et al. 1992), and chemoreceptor cells of the rabbit carotid Body are excitable cells with voltage-dependent Na+, K+ and Ca2+ channels (Duchen et al. 1988; Lopez-Barneo et al. 1988). Similar voltage-dependent channels are also seen in the neuroendocrine cells of the airway neuroepithelial bodies (Youngson et al. 1993). The mechanisms by which the type I cells of the carotid Body respond to changes in PO2 remain uncertain. In type I cells, a voltage-activated K+ current has been proposed to be inhibited by hypoxia (oxygen-sensitive K+ current) (Lopez-Barneo et al. 1988; Delpiano & Hescheler, 1989; Peers, 1990a). A similar oxygen-sensitive K+ current has been found in the neuroendocrine cells of the airway neuroepithelial bodies (Youngson et al. 1993), neonatal adrenal chromaffin cells (Thompson et al. 1997) and PC12 cells (Conforti & Millhorn, 1997). Quite recently, however, a novel oxygen-sensitive K+ current was reported in rat carotid Body type I cells, in which hypoxia inhibited voltage-insensitive resting K+ conductance (Buckler, 1997). Epithelioid cells containing 5-HT are aggregated into clusters and form a band of about 1 mm in width in the wall of the chicken thoracic aorta (Miyoshi et al. 1995). We have suggested that these cells are arterial chemoreceptors corresponding to the mammalian Aortic Body because hypoxic stimulation causes the release of 5-HT from pieces of chicken thoracic aorta (Ito et al. 1997). In comparison with the knowledge of properties of carotid chemoreceptor cells, less is known about the characteristics of chemoreceptor cells in the Aortic Body. Leech neurons containing catecholamines or 5-HT have been shown to be stained with a vital dye, Neutral Red (Stuart et al. 1974). Using this dye, it is possible that epithelioid cells containing 5-HT could be identified after dissociation from the chicken thoracic aorta. In the present experiments, we firstly examined whether or not Neutral Red-positive cells isolated from the chicken thoracic aorta contained 5-HT, and then examined the types of voltage-activated channels and oxygen-sensitive channels in Neutral Red-positive epithelioid cells using the whole-cell patch clamp technique. We also investigated characteristics of 5-HT secretion evoked by veratridine and excess KCl from pieces of chicken thoracic aorta.