Background leak K+-currents and oxygen sensing in carotid body type 1 cells

Carotid body (CB) type I cells sense the blood Po2 and generate a nervous signal for stimulating ventilation and circulation when blood oxygen levels decline. Three oxygen-sensing enzyme complexes may be used for this purpose: 1) mitochondrial electron transport chain metabolism, 2) heme oxygenase 2 (HO-2)-generating CO, and/or 3) an NAD(P)H oxidase (NOX). We hypothesize that intracellular redox changes are the link between the sensor and nervous signals. To test this hypothesis type I cell autofluorescence of flavoproteins (Fp) and NAD(P)H within the mouse CB ex vivo was recorded as Fp/(Fp+NAD(P)H) redox ratio. CB type I cell redox ratio transiently declined with the onset of hypoxia. Upon reoxygenation, CB type I cells showed a significantly increased redox ratio. As a control organ, the non-oxygen-sensing sympathetic superior cervical ganglion (SCG) showed a continuously reduced redox ratio upon hypoxia. CN−, diphenyleneiodonium, or reactive oxygen species influenced chemoreceptor discharge (CND) with subsequent loss of O2 sensitivity and inhibited hypoxic Fp reduction only in the CB but not in SCG Fp, indicating a specific role of Fp in the oxygen-sensing process. Hypoxia-induced changes in CB type I cell redox ratio affected peptidyl prolyl isomerase Pin1, which is believed to colocalize with the NADPH oxidase subunit p47phox in the cell membrane to trigger the opening of potassium channels. We postulate that hypoxia-induced changes in the Fp-mediated redox ratio of the CB regulate the Pin1/p47phox tandem to alter type I cell potassium channels and therewith CND.

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Biophysical properties and metabolic regulation of a TASK-like potassium channel in rat carotid body type 1 cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00010.2003 ◽

2004 ◽

Vol 286 (1) ◽

pp. L221-L230 ◽

Cited By ~ 50

Author(s):

Beatrice A. Williams ◽

Keith J. Buckler

Keyword(s):

Potassium Channel ◽

Carotid Body ◽

Metabolic Regulation ◽

Single Channel ◽

Divalent Cations ◽

Channel Activity ◽

Body Type ◽

Oxygen Sensitive ◽

Inside Out

The single channel properties of TASK-like oxygen-sensitive potassium channels were studied in rat carotid body type 1 cells. We observed channels with rapid bursting kinetics, active at resting membrane potentials. These channels were highly potassium selective with a slope conductance of 14–16 pS, values similar to those reported for TASK-1. In the absence of extracellular divalent cations, however, single channel conductance increased to 28 pS in a manner similar to that reported for TASK-3. After patch excision, channel activity ran down rapidly. Channel activity in inside-out patches was markedly increased by 2 and 5 mM ATP and by 2 mM ADP but not by 100 μM ADP or 1 mM AMP. In cell-attached patches, both cyanide and 2,4-dinitrophenol strongly inhibited channel activity. We conclude that 1) whilst the properties of this channel are consistent with it being a TASK-like potassium channel they do not precisely conform to those of either TASK-1 or TASK-3, 2) channel activity is highly dependent on cytosolic factors including ATP, and 3) changes in energy metabolism may play a role in regulating the activity of these background K+ channels.

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Synapse Formation and Hypoxic Signalling in Co-Cultures of Rat Petrosal Neurones and Carotid Body Type 1 Cells

The Journal of Physiology ◽

10.1111/j.1469-7793.1997.599bg.x ◽

1997 ◽

Vol 503 (3) ◽

pp. 599-612 ◽

Cited By ~ 68

Author(s):

Huijun Zhong ◽

Min Zhang ◽

Colin A. Nurse

Keyword(s):

Carotid Body ◽

Synapse Formation ◽

Body Type

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Co-Cultures of Rat Petrosal Neurons and Carotid Body Type 1 Cells

Frontiers in Arterial Chemoreception - Advances in Experimental Medicine and Biology ◽

10.1007/978-1-4615-5891-0_27 ◽

1996 ◽

pp. 189-193 ◽

Cited By ~ 5

Author(s):

Huijun Zhong ◽

Colin Nurse

Keyword(s):

Carotid Body ◽

Body Type

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Ca2+ oscillations in rat carotid body type 1 cells in normoxia and hypoxia

AJP Cell Physiology ◽

10.1152/ajpcell.00442.2019 ◽

2020 ◽

Vol 318 (2) ◽

pp. C430-C438

Author(s):

Donghee Kim ◽

James O. Hogan ◽

Carl White

Keyword(s):

Carotid Body ◽

Low Frequency ◽

Body Type ◽

Intrinsic Frequency ◽

Signaling Mechanism ◽

Mean Frequency ◽

Inositol 1,4,5 Trisphosphate ◽

The Mean ◽

Trisphosphate Receptor

We studied the mechanisms by which carotid body glomus (type 1) cells produce spontaneous Ca2+ oscillations in normoxia and hypoxia. In cells perfused with normoxic solution at 37°C, we observed relatively uniform, low-frequency Ca2+ oscillations in >60% of cells, with each cell showing its own intrinsic frequency and amplitude. The mean frequency and amplitude of Ca2+ oscillations were 0.6 ± 0.1 Hz and 180 ± 42 nM, respectively. The duration of each Ca2+ oscillation ranged from 14 to 26 s (mean of ∼20 s). Inhibition of inositol (1,4,5)-trisphosphate receptor and store-operated Ca2+ entry (SOCE) using 2-APB abolished Ca2+ oscillations. Inhibition of endoplasmic reticulum Ca2+-ATPase (SERCA) using thapsigargin abolished Ca2+ oscillations. ML-9, an inhibitor of STIM1 translocation, also strongly reduced Ca2+ oscillations. Inhibitors of L- and T-type Ca2+ channels (Cav; verapamil>nifedipine>TTA-P2) markedly reduced the frequency of Ca2+ oscillations. Thus, Ca2+ oscillations observed in normoxia were caused by cyclical Ca2+ fluxes at the ER, which was supported by Ca2+ influx via Ca2+ channels. Hypoxia (2–5% O2) increased the frequency and amplitude of Ca2+ oscillations, and Cav inhibitors (verapamil>nifedipine>>TTA-P2) reduced these effects of hypoxia. Our study shows that Ca2+ oscillations represent the basic Ca2+ signaling mechanism in normoxia and hypoxia in CB glomus cells.

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