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

Hempleman, Steven C.; Adamson, T.P.; Begay, Rowin S.; Solomon, Irene C.

doi:10.1152/ajpregu.00519.2002

Cited by 17 publications

(3 citation statements)

References 51 publications

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“…Very little is known about the ion channels in IPC, but to explain the backwards relationship between pH i and IPC firing rate, it has been hypothesized that IPC contain K ϩ channels that are opened by decreased pH i and/or Ca 2ϩ or Na ϩ channels that are inhibited by decreased pH i (149,150). The development of an experimental cellular model of IPC would be most helpful in further characterizing the signaling in these unusual CO 2 /H ϩ -responsive cells and would allow direct measurements of pH i and the channels involved in chemosensitive signaling.…”

Section: Other Acid-sensitive Cellsmentioning

confidence: 99%

Cellular mechanisms involved in CO₂ and acid signaling in chemosensitive neurons

Putnam

Filosa

Ritucci

2004

American Journal of Physiology-Cell Physiology

277

343

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An increase in CO(2)/H(+) is a major stimulus for increased ventilation and is sensed by specialized brain stem neurons called central chemosensitive neurons. These neurons appear to be spread among numerous brain stem regions, and neurons from different regions have different levels of chemosensitivity. Early studies implicated changes of pH as playing a role in chemosensitive signaling, most likely by inhibiting a K(+) channel, depolarizing chemosensitive neurons, and thereby increasing their firing rate. Considerable progress has been made over the past decade in understanding the cellular mechanisms of chemosensitive signaling using reduced preparations. Recent evidence has pointed to an important role of changes of intracellular pH in the response of central chemosensitive neurons to increased CO(2)/H(+) levels. The signaling mechanisms for chemosensitivity may also involve changes of extracellular pH, intracellular Ca(2+), gap junctions, oxidative stress, glial cells, bicarbonate, CO(2), and neurotransmitters. The normal target for these signals is generally believed to be a K(+) channel, although it is likely that many K(+) channels as well as Ca(2+) channels are involved as targets of chemosensitive signals. The results of studies of cellular signaling in central chemosensitive neurons are compared with results in other CO(2)- and/or H(+)-sensitive cells, including peripheral chemoreceptors (carotid body glomus cells), invertebrate central chemoreceptors, avian intrapulmonary chemoreceptors, acid-sensitive taste receptor cells on the tongue, and pain-sensitive nociceptors. A multiple factors model is proposed for central chemosensitive neurons in which multiple signals that affect multiple ion channel targets result in the final neuronal response to changes in CO(2)/H(+).

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Section: Other Acid-sensitive Cellsmentioning

confidence: 99%

Cellular mechanisms involved in CO₂ and acid signaling in chemosensitive neurons

Putnam

Filosa

Ritucci

2004

American Journal of Physiology-Cell Physiology

277

343

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“…In applying the assumption to acute metabolic disturbances, we reasoned that because IPC express several acid-base transporters, they should be able to employ several mechanisms capable of rapidly modifying intracellular pH. Recent experimental evidence demonstrates that stilbene-sensitive HCO 3 Ϫ /Cl Ϫ anion exchangers (30) and amiloride-sensitive Na ϩ /H ϩ antiports (16) participate in modulating IPC activity during step changes in CO 2 , thus lending support to this idea. In addition, several experiments indicate that IPC are sensitive to rapid intravenous infusions of HCl or NaHCO 3 , which suggests that some degree Fig.…”

Section: Critique: Estimating Intracellular Ph From Extracellular Phmentioning

confidence: 99%

Effects of aerobic and anaerobic metabolic inhibitors on avian intrapulmonary chemoreceptors

Pilarski¹,

Solomon²,

Kilgore³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Birds have rapidly responding respiratory chemoreceptors [intrapulmonary chemoreceptors (IPC)] that provide vagal sensory feedback about breathing pattern. IPC are exquisitely sensitive to CO(2) but are unaffected by hypoxia. IPC continue to respond to CO(2) during hypoxic and even anoxic conditions, suggesting that they may generate ATP needed for signal transduction anaerobically. To assess IPC energy metabolism, single-cell action potential discharge and acid-base status were recorded from 26 pentobarbital-anesthetized Anas platyrhynchos before and after intravenous infusion of the glycolytic blocker iodoacetate (10-70 mg/kg), mitochondrial blocker rotenone (2 mg/kg), and/or mitochondrial uncoupler 2,4-dinitrophenol (5-15 mg/kg). After 5 min exposure at the highest dosages, iodoacetate inhibited IPC discharge 65% (15.9 +/- 0.3 s(-1) to 5.5 +/- 0.3 s(-1), P < 0.05), rotenone inhibited discharge 80% (12.9 +/- 0.5 s(-1) to 2.6 +/- 0.6 s(-1), P < 0.05), and 2,4-dinitrophenol inhibited discharge 19% (14.0 +/- 0.3 s(-1) to 11.3 +/- 0.3 s(-1), P < 0.05). These results suggest that IPC utilize glucose, require an intact glycolytic pathway, and metabolize the products of glycolysis to CO(2) and H(2)O by mitochondrial respiration. The small but significant effect of 2,4-dinitrophenol suggests that ATP production by glycolysis may be sufficient to meet IPC energy demands if NADH can be oxidized to NAD experimentally by uncoupling mitochondria, or physiologically by transient lactate production. A model for IPC spike frequency adaptation is proposed, whereby the rapid onset of phasic IPC discharge requires ATP from anaerobic glycolysis, using lactate as the electron acceptor, and the roll-off in IPC discharge reflects transient acidosis due to intracellular lactic acid accumulation.

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“…Ϫ ; thus the actual IPC stimulus appears to be the products of CO 2 hydration. IPC signal transduction involves Na ϩ /H ϩ antiports [since blockade with dimethyl amiloride depresses IPC discharge (8)], and HCO 3…”

mentioning

confidence: 99%

Calcium and avian intrapulmonary chemoreceptor response to CO₂

Hempleman

Egan

Pilarski

et al. 2006

Journal of Applied Physiology

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Intrapulmonary chemoreceptors (IPC) are highly responsive respiratory chemoreceptors that innervate the lungs of birds and diapsid reptiles. IPC are stimulated by low levels of lung Pco(2), inhibited by high levels of lung Pco(2), and their vagal afferents serve as a sensory limb for reflex adjustments of breathing depth and rate. Most IPC exhibit both phasic and tonic sensitivity to CO(2), and spike frequency adaptation (SFA) contributes to their phasic CO(2) responsiveness. To test whether CO(2) responsiveness and SFA in IPC is modulated by a Ca(2+)-linked mechanism, we quantified the role of transmembrane Ca(2+) fluxes and Ca(2+)-related channels on single-unit IPC function in response to phasic changes in inspired Pco(2). We found that 1) broad-spectrum blockade of Ca(2+) channels using cadmium or cobalt and blockade of L-type Ca(2+) channels using nifedipine increased IPC discharge; 2) activation of L-type Ca(2+) channels using BAY K 8644 reduced IPC discharge; 3) blockade of Ca(2+)-activated potassium channels using charybdotoxin (antagonist of large-conductance Ca(2+)-dependent K(+) channel) increased IPC discharge, but neither charybdotoxin nor apamin affected SFA; and 4) blockade of chloride channels, including Ca(2+)-activated chloride channels, with niflumic acid decreased IPC discharge at low Pco(2) and increased IPC discharge at high Pco(2), resulting in a net attenuation of the IPC CO(2) response. We conclude that Ca(2+) influx through L-type Ca(2+) channels has an inhibitory effect on IPC afferent discharge and CO(2) sensitivity, that spike frequency adaptation is not due to apamin- or charybdotoxin-sensitive Ca(2+)-activated K(+) channels in IPC, and that chloride channels blocked by niflumic acid help modulate IPC CO(2) responses.

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

Cited by 17 publications

References 51 publications

Cellular mechanisms involved in CO₂ and acid signaling in chemosensitive neurons

Cellular mechanisms involved in CO₂ and acid signaling in chemosensitive neurons

Effects of aerobic and anaerobic metabolic inhibitors on avian intrapulmonary chemoreceptors

Calcium and avian intrapulmonary chemoreceptor response to CO₂

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

Cited by 17 publications

References 51 publications

Cellular mechanisms involved in CO2 and acid signaling in chemosensitive neurons

Cellular mechanisms involved in CO2 and acid signaling in chemosensitive neurons

Effects of aerobic and anaerobic metabolic inhibitors on avian intrapulmonary chemoreceptors

Calcium and avian intrapulmonary chemoreceptor response to CO2

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Product

Resources

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

Cellular mechanisms involved in CO₂ and acid signaling in chemosensitive neurons

Cellular mechanisms involved in CO₂ and acid signaling in chemosensitive neurons

Calcium and avian intrapulmonary chemoreceptor response to CO₂