Presynaptic regulation of isolated neonatal rat carotid body type I cells by histamine

Burlon, Drew C.; Jordan, Heidi L.; Wyatt, Christopher N.

doi:10.1016/j.resp.2009.07.002

Cited by 12 publications

(6 citation statements)

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“…Baseline fluorescence was usually noisy when gassing with 10% rather than 21% O 2 (see Burlon et al . () for examples of quiet baselines at 21%) but 100% of cells recorded from responded rapidly with a rise in the fluorescence ratio when exposed to HC. The second exposure to HC was smaller than the first (see Fig.…”

Section: Resultsmentioning

confidence: 98%

Adrenaline release evokes hyperpnoea and an increase in ventilatory CO₂ sensitivity during hypoglycaemia: a role for the carotid body

Thompson

Ray

Holmes

et al. 2016

The Journal of Physiology

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Key pointsr Hypoglycaemia is counteracted by release of hormones and an increase in ventilation and CO 2 sensitivity to restore blood glucose levels and prevent a fall in blood pH.r The full counter-regulatory response and an appropriate increase in ventilation is dependent on carotid body stimulation.r We show that the hypoglycaemia-induced increase in ventilation and CO 2 sensitivity is abolished by preventing adrenaline release or blocking its receptors.r Physiological levels of adrenaline mimicked the effect of hypoglycaemia on ventilation and CO 2 sensitivity.r These results suggest that adrenaline, rather than low glucose, is an adequate stimulus for the carotid body-mediated changes in ventilation and CO 2 sensitivity during hypoglycaemia to prevent a serious acidosis in poorly controlled diabetes.Abstract Hypoglycaemia in vivo induces a counter-regulatory response that involves the release of hormones to restore blood glucose levels. Concomitantly, hypoglycaemia evokes a carotid body-mediated hyperpnoea that maintains arterial CO 2 levels and prevents respiratory acidosis in the face of increased metabolism. It is unclear whether the carotid body is directly stimulated by low glucose or by a counter-regulatory hormone such as adrenaline. Minute ventilation was recorded during infusion of insulin-induced hypoglycaemia (8-17 mIU kg −1 min −1 ) in Alfaxan-anaesthetised male Wistar rats. Hypoglycaemia significantly augmented minute ventilation (123 ± 4 to 143 ± 7 ml min −1 ) and CO 2 sensitivity (3.3 ± 0.3 to 4.4 ± 0.4 ml min −1 mmHg −1 ). These effects were abolished by either β-adrenoreceptor blockade with propranolol or adrenalectomy. In this hypermetabolic, hypoglycaemic state, propranolol stimulated a rise in P aCO 2 , suggestive of a ventilation-metabolism mismatch. Infusion of adrenaline (1 μg kg −1 min −1 ) increased minute ventilation (145 ± 4 to 173 ± 5 ml min −1 ) without altering P aCO 2 or pH and enhanced ventilatory CO 2 sensitivity (3.4 ± 0.4 to 5.1 ± 0.8 ml min −1 mmHg −1 ). These effects were attenuated by either resection of the carotid sinus nerve or propranolol. Physiological concentrations of adrenaline increased the CO 2 sensitivity of freshly dissociated carotid body type I cells in vitro. These findings suggest that adrenaline release can account for the ventilatory hyperpnoea observed during hypoglycaemia by an augmented carotid body and whole body ventilatory CO 2 sensitivity.

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Section: Resultsmentioning

confidence: 98%

Adrenaline release evokes hyperpnoea and an increase in ventilatory CO₂ sensitivity during hypoglycaemia: a role for the carotid body

Thompson

Ray

Holmes

et al. 2016

The Journal of Physiology

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“…Carotid bodies and then Type I cells were isolated from ninety two rats across nine litters. Carotid bodies were resected from anesthetized (5% isoflurane in oxygen; 1 L/min) neonatal Sprague-Dawley rats (11–23 days old) before the sedated animals were euthanized via decapitation, see Burlon et al (2009) . Carotid bodies were held in ice-cold Dulbecco’s Phosphate Buffered Saline (DPBS; without calcium or magnesium, Gibco) before Type I cells were dissociated using a digestive enzyme solution composed of: 4mg of collagenase type I (220-240 u/mg, Worthington), and 2mg trypsin from bovine pancreas (8000-12,000 u/mg, Sigma) dissolved in 9.65 ml of DPBS (0.65 ml with calcium and magnesium, 9 ml without calcium and magnesium; Gibco).…”

Section: Methodsmentioning

confidence: 99%

“…Cells were held in an incubator at 37°C, 5% CO 2 in humidified air until used for experimentation (2–6 h). These methods reliably isolate viable CB Type I cells that retain their oxygen-sensitivity ( Burlon et al, 2009 ).…”

Section: Methodsmentioning

confidence: 99%

Acute Oxygen-Sensing via Mitochondria-Generated Temperature Transients in Rat Carotid Body Type I Cells

2022

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The Carotid Bodies (CB) are peripheral chemoreceptors that detect changes in arterial oxygenation and, via afferent inputs to the brainstem, correct the pattern of breathing to restore blood gas homeostasis. Herein, preliminary evidence is presented supporting a novel oxygen-sensing hypothesis which suggests CB Type I cell “hypoxic signaling” may in part be mediated by mitochondria-generated thermal transients in TASK-channel-containing microdomains. Distances were measured between antibody-labeled mitochondria and TASK-potassium channels in primary rat CB Type I cells. Sub-micron distance measurements (TASK-1: 0.33 ± 0.04 µm, n = 47 vs TASK-3: 0.32 ± 0.03 µm, n = 54) provided evidence for CB Type I cell oxygen-sensing microdomains. A temperature-sensitive dye (ERthermAC) indicated that inhibition of mitochondrial activity in isolated cells caused a rapid and reversible inhibition of mitochondrial thermogenesis and thus temperature in these microdomains. Whole-cell perforated-patch current-clamp electrophysiological recordings demonstrated sensitivity of resting membrane potential (Vm) to temperature: lowering bath temperature from 37°C to 24°C induced consistent and reversible depolarizations (Vm at 37°C: 48.4 ± 4.11 mV vs 24°C: 31.0 ± 5.69 mV; n = 5; p < 0.01). These data suggest that hypoxic inhibition of mitochondrial thermogenesis may play an important role in oxygen chemotransduction in the CB. A reduction in temperature within cellular microdomains will inhibit plasma membrane ion channels, influence the balance of cellular phosphorylation–dephosphorylation, and may extend the half-life of reactive oxygen species. The characterization of a thermosensory chemotransduction mechanism, that may also be used by other oxygen-sensitive cell types and may impact multiple other chemotransduction mechanisms is critical if we are to fully understand how the CBs, and potentially other oxygen-sensitive cells, respond to hypoxia.

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“…Cells were used within 8 h after being dissected. These methods yield isolated carotid body type I cells that remain oxygen-sensitive [ 18 ].…”

Section: Type I Cell Isolationmentioning

confidence: 99%

“…Extracellular solution was HEPES buffered salt solution. The high K + stimulus was (in mM): 64.5 NaCl, 80 KCl, 2.5 CaCl 2 , 1, MgCl 2 , 11 glucose, 10 HEPES adjusted to pH 7.4 with KOH at 37 °C [ 4 , 18 ]. DAMGO-Enkephalin acetate salt was dissolved in double-distilled water before being aliquoted, frozen (−20 ° C), and then thawed before use.…”

Section: Type I Cell Isolationmentioning

confidence: 99%

Ethanol and opioids do not act synergistically to depress excitation in carotid body type I cells

Rakoczy

Kamra²,

Yi³

et al. 2021

NeuroReport

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Objective The combination of opioids and ethanol can synergistically depress breathing and the acute ventilatory response to hypoxia. Multiple studies have shown that the underlying mechanisms for this may involve calcium channel inhibition in central neurons. But we have previously identified opioid receptors in the carotid bodies and shown that their activation inhibits calcium influx into the chemosensitive cells. Given that the carotid bodies contribute to the drive to breathe and underpin the acute hypoxic ventilatory response, we hypothesized that ethanol and opioids may act synergistically in these peripheral sensory organs to further inhibit calcium influx and therefore inhibit ventilation. Methods Carotid bodies were removed from 56 Sprague–Dawley rats (1021 days old) and then enzymatically dissociated to allow calcium imaging of isolated chemosensitive type I cells. Cells were stimulated with high K + in the presence and absence of the µ-opioid agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) (10 µM), a maximal sublethal concentration of ethanol (3 g L -1 , 65.1 mM) or a combination of both. Results DAMGO alone significantly inhibited Ca 2+ influx but this effect was not potentiated by the high concentration of ethanol. Conclusion These results indicate for the first time that while opioids may suppress breathing via an action at the level of the carotid bodies, ethanol is unlikely to potentiate inhibition via this pathway. Thus, the synergistic effects of ethanol and opioids on ventilatory parameters are likely mediated by central rather than peripheral actions.

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Presynaptic regulation of isolated neonatal rat carotid body type I cells by histamine

Cited by 12 publications

References 59 publications

Adrenaline release evokes hyperpnoea and an increase in ventilatory CO₂ sensitivity during hypoglycaemia: a role for the carotid body

Adrenaline release evokes hyperpnoea and an increase in ventilatory CO₂ sensitivity during hypoglycaemia: a role for the carotid body

Acute Oxygen-Sensing via Mitochondria-Generated Temperature Transients in Rat Carotid Body Type I Cells

Ethanol and opioids do not act synergistically to depress excitation in carotid body type I cells

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Presynaptic regulation of isolated neonatal rat carotid body type I cells by histamine

Cited by 12 publications

References 59 publications

Adrenaline release evokes hyperpnoea and an increase in ventilatory CO2 sensitivity during hypoglycaemia: a role for the carotid body

Adrenaline release evokes hyperpnoea and an increase in ventilatory CO2 sensitivity during hypoglycaemia: a role for the carotid body

Acute Oxygen-Sensing via Mitochondria-Generated Temperature Transients in Rat Carotid Body Type I Cells

Ethanol and opioids do not act synergistically to depress excitation in carotid body type I cells

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Product

Resources

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Adrenaline release evokes hyperpnoea and an increase in ventilatory CO₂ sensitivity during hypoglycaemia: a role for the carotid body

Adrenaline release evokes hyperpnoea and an increase in ventilatory CO₂ sensitivity during hypoglycaemia: a role for the carotid body