Laryngeal CO2 receptors: influence of systemic PCO and carbonic anhydrase inhibition

Coates, E. L.; Knuth, Susan L.; Bartlett, D.

doi:10.1016/0034-5687(96)00009-6

Cited by 35 publications

(26 citation statements)

References 20 publications

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“…In carotid body type 1 cells, inhibition of CA delayed the onset of, and reduced the magnitude of chemosensory responses to CO 2 (Iturriaga, 1993). Similarly, CA inhibition reduced the discharge rate from laryngeal receptors (Coates et al, 1996) and blunted central chemosensory responses to elevated CO 2 in the cat (Coates et al, 1991).…”

Section: Research Articlementioning

confidence: 88%

Cardiac responses to hypercapnia in larval zebrafish (Danio rerio): The links between CO2 chemoreception, catecholamines and carbonic anhydrase

Miller

Pollack

Bradshaw

et al. 2014

Journal of Experimental Biology

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The ontogeny of carbon dioxide (CO 2 ) sensing in zebrafish (Danio rerio) has not been examined. In this study, CO 2 -mediated increases in heart rate were used to gauge the capacity of zebrafish larvae to sense CO 2 . CO 2 is thought to be detected via neuroepithelial cells (NECs), which are homologous to mammalian carotid body glomus cells. Larvae at 5 days post-fertilization (d.p.f.) exhibited tachycardia when exposed for 30 min to 0.75% CO 2 (~5.63 mmHg); at 7 d.p.f., tachycardia was elicited by 0.5% CO 2 (~3.75 mmHg). Based on pharmacological evidence using β-adrenergic receptor (β-AR) antagonists, and confirmed by β 1 -AR translational gene knockdown using morpholinos, the reflex tachycardia accompanying hypercapnia was probably mediated by the interaction of catecholamines with cardiac β 1 receptors. Because the cardiac response to hypercapnia was abolished by the ganglionic blocker hexamethonium, it is probable that the reflex cardio-acceleration was mediated by catecholamines derived from sympathetic adrenergic neurons. Owing to its likely role in facilitating intracellular acidification during exposure to hypercapnia, it was hypothesized that carbonic anhydrase (CA) is involved in CO 2 sensing, and that inhibition of CA activity would blunt the downstream responses. Indeed, the cardiac response to hypercapnia (0.75% CO 2 ) was reduced in fish at 5 d.p.f. exposed to acetazolamide, a CA inhibitor, and in fish experiencing zCAc (CA2-like a) knockdown. Successful knockdown of zCAc was confirmed by CA activity measurements, western blotting and immunocytochemistry. Co-injection of embryos with zCAc morpholino and mRNA modified at the morpholino binding site restored normal levels of CA activity and protein levels, and restored (rescued) the usual cardiac responses to hypercapnia. These data, combined with the finding that zCAc is expressed in NECs located on the skin, suggest that the afferent limb of the CO 2 -induced cardiac reflex in zebrafish larvae is initiated by coetaneous CO 2 -sensing neuroepithelial cells.

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Section: Research Articlementioning

confidence: 88%

Cardiac responses to hypercapnia in larval zebrafish (Danio rerio): The links between CO2 chemoreception, catecholamines and carbonic anhydrase

Miller

Pollack

Bradshaw

et al. 2014

Journal of Experimental Biology

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“…administration of methazolamide in one of the two tonically active receptors studied in this report. Also, in a study by Coates et al (1996), the inhibitory effects of CO 2 in nine of the 10 receptors examined were diminished by I.V. administration of acetazolamide and these receptors generally had tonic baseline activity.…”

Section: Discussionmentioning

confidence: 99%

“…administration of methazolamide appears to be a more effective means of CA inhibition than luminal application. Indeed Coates et al (1996) found that luminal application of acetazolamide had little effect on the inhibition of activity caused by CO 2 on tonically active laryngeal receptors but that I.V. administration was effective in attenuating this inhibitory effect.…”

Section: Discussionmentioning

confidence: 99%

“…There is also evidence that CA may participate in the response to CO 2 of pulmonary stretch receptors (Sant'Ambrogio et al 1974), in the responses of the lingual trigeminal nerve to CO 2 (Komai & Bryant, 1993) and in the inhibitory effect of CO 2 on tonically active laryngeal receptors (Coates et al 1996). CA has been localised histochemically in areas where laryngeal receptors are located (Wang et al 1994), namely the laryngeal surface epithelium and the nearby sensory nerve endings.…”

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confidence: 99%

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Effects of Carbonic Anhydrase Inhibition on the Responsiveness of Laryngeal Receptors in Cats to CO₂

Wang

Bradford

O’Regan

2001

Experimental Physiology

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The effects of carbonic anhydrase inhibition on the responsiveness to CO 2 of pressure-sensitive laryngeal receptors were examined in anaesthetised, paralysed cats. Laryngeal CO 2 -sensitive receptors from the superior laryngeal nerve were selected by their responsiveness to intralaryngeal pressure and to perfusion of solution equilibrated with 9 % CO 2 . The carbonic anhydrase inhibitor, methazolamide, when given intralaryngeally at 10 _4 M, diminished or abolished the responses to the CO 2 -equilibrated solution in four of six pressure-sensitive receptors. Histochemical staining for carbonic anhydrase activity showed that the larynges perfused with methazolamide had diminished carbonic anhydrase activity, especially on the superficial layers of surface epithelium. Compared to untreated controls, when given intravenously (50 mg kg

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“…Low PCO 2 stimulates IPC firing, and high PCO 2 inhibits firing (9, 15, 16); thus the IPC response is backward compared with that of traditional respiratory chemoreceptors like the carotid bodies (18, 29), many presumptive central chemoreceptors (40), and snail pneumostome ganglia chemoreceptors (13,14). Many presumptive chemoreceptor neurons located in the mammalian medullary raphe, however, have also been shown to be inhibited by high PCO 2 (41, 54), as are reptilian IPC, mammalian pulmonary stretch receptors, and mammalian laryngeal CO 2 chemoreceptors (10,32,39,44). Thus the inverse CO 2 response (discharge rate inhibited by high CO 2 ) may be a common variant of respiratory chemosensitivity, just somewhat overlooked.…”

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confidence: 99%

CO₂transduction in avian intrapulmonary chemoreceptors is critically dependent on transmembrane Na⁺/H⁺exchange

Hempleman

Adamson

Begay

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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R1551-R1559, 2003. First published February 20, 2003 10.1152/ajpregu.00519.2002Avian intrapulmonary chemoreceptors (IPC) are vagal respiratory afferents that are inhibited by high lung PCO 2 and excited by low lung PCO 2. Previous work suggests that increased CO 2 inhibits IPC by acidifying intracellular pH (pHi) and that pH i is determined by a kinetic balance between the rate of intracellular carbonic anhydrase-catalyzed CO 2 hydration/dehydration and transmembrane extrusion of acids and/or bases by various exchangers. Here, the role of amiloride-sensitive Na ϩ /H ϩ exchange (NHE) in the IPC CO2 response was tested by recording single-unit action potentials from IPC in anesthetized ducks, Anas platyrhynchos. For each of the IPC tested, blockade of the NHE using dimethyl amiloride (DMA) elicited a marked (Ͼ50%) dose-dependent decrease in mean IPC discharge (P Ͻ 0.05), suggesting that NHE is important for pH i regulation and CO2 transduction in IPC. In addition, activation of the NHE using 12-O-tetradecanoylphorbol 13-acetate stimulated six of the seven IPC tested, although the overall effect was not statistically significantly (P ϭ 0.07). Taken together, these findings suggest that CO 2 transduction in IPC is dependent on transmembrane NHE although it is likely to be much slower than carbonic anhydrase-catalyzed hydration-dehydration of CO2. carbon dioxide chemosensitivity; intracellular pH regulation; respiratory control; neuron; acid; base BIRDS HAVE INTRAPULMONARY chemoreceptors (IPC) that monitor lung PCO 2 and exert reflex effects on the pattern of breathing (9,15,16,36,37,43,45). These IPC have afferent axons in the vagus nerves, cell bodies in the nodose ganglia, and sensory endings in the parabronchial tissue of the lungs (9, 25, 34). The action potential discharge of IPCs responds to both rapidly changing (i.e., phasic) and sustained (or tonic) levels of intrapulmonary PCO 2 , thereby encoding information about the temporal relationships between ventilation, perfusion, and metabolism (4,9,15,16,19,24,34). IPC sensory feedback helps terminate inspiration by sensing CO 2 washout from the lung, helps maintain arterial homeostasis in response to moderate inspired hypercapnia (35,37,45), and helps adjust breathing to metabolic demands (4,9,19,24,50).IPC are unusual respiratory chemoreceptors because their action potential discharge rate is inversely proportional to intrapulmonary PCO 2 . Low PCO 2 stimulates IPC firing, and high PCO 2 inhibits firing (9, 15, 16); thus the IPC response is backward compared with that of traditional respiratory chemoreceptors like the carotid bodies (18, 29), many presumptive central chemoreceptors (40), and snail pneumostome ganglia chemoreceptors (13,14). Many presumptive chemoreceptor neurons located in the mammalian medullary raphe, however, have also been shown to be inhibited by high PCO 2 (41, 54), as are reptilian IPC, mammalian pulmonary stretch receptors, and mammalian laryngeal CO 2 chemoreceptors (10,32,39,44). Thus the inverse CO 2 response (discharge rate inhi...

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Laryngeal CO2 receptors: influence of systemic PCO and carbonic anhydrase inhibition

Cited by 35 publications

References 20 publications

Cardiac responses to hypercapnia in larval zebrafish (Danio rerio): The links between CO2 chemoreception, catecholamines and carbonic anhydrase

Cardiac responses to hypercapnia in larval zebrafish (Danio rerio): The links between CO2 chemoreception, catecholamines and carbonic anhydrase

Effects of Carbonic Anhydrase Inhibition on the Responsiveness of Laryngeal Receptors in Cats to CO₂

CO₂transduction in avian intrapulmonary chemoreceptors is critically dependent on transmembrane Na⁺/H⁺exchange

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Laryngeal CO2 receptors: influence of systemic PCO and carbonic anhydrase inhibition

Cited by 35 publications

References 20 publications

Cardiac responses to hypercapnia in larval zebrafish (Danio rerio): The links between CO2 chemoreception, catecholamines and carbonic anhydrase

Cardiac responses to hypercapnia in larval zebrafish (Danio rerio): The links between CO2 chemoreception, catecholamines and carbonic anhydrase

Effects of Carbonic Anhydrase Inhibition on the Responsiveness of Laryngeal Receptors in Cats to CO2

CO2transduction in avian intrapulmonary chemoreceptors is critically dependent on transmembrane Na+/H+exchange

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Effects of Carbonic Anhydrase Inhibition on the Responsiveness of Laryngeal Receptors in Cats to CO₂

CO₂transduction in avian intrapulmonary chemoreceptors is critically dependent on transmembrane Na⁺/H⁺exchange