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Query: UMLS:C0242706 (
hyperoxia
)
5,219
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The carotid body is a peripheral sensory organ that can transduce modest falls in the arterial PO(2) (partial pressure of oxygen) into a neural signal that provides the afferent limb of a set of stereotypic cardiorespiratory reflexes that are graded according to the intensity of the stimulus. The stimulus sensed is tissue PO(2) and this can be estimated to be around 50 mmHg during arterial normoxia, falling to between 10-40 mmHg during hypoxia. The chemoafferent hypoxia stimulus-response curve is exponential, rising in discharge frequency with falling PO(2), and with no absolute threshold apparent in
hyperoxia
. Although the oxygen sensor has not been definitely identified, it is believed to reside within type I cells of the carotid body, and presently two major hypotheses have been put forward to account for the sensing mechanism. The first relies upon alterations in the cell energy status that is sensed by the cytosolic enzyme AMPK (AMP-activated protein kinase) subsequent to hypoxia-induced increases in the cellular AMP/ATP ratio during hypoxia. AMPK is localized close to the plasma membrane and its activation can inhibit both large conductance, calcium-activated potassium (BK) and background,
TASK
-like potassium channels, inducing membrane depolarization, voltage-gated calcium entry and neurosecretion of a range of transmitter and modulator substances, including catecholamines, ATP and acetylcholine. The alternative hypothesis considers a role for haemoxygenase-2, which uses oxygen as a substrate and may act to gate an associated BK channel through the action of its products, carbon monoxide and possibly haem. It is likely however, that these and other hypotheses of oxygen transduction are not mutually exclusive and that each plays a role, via its own particular sensitivity, in shaping the full response of this organ between
hyperoxia
and anoxia.
...
PMID:Sensing hypoxia in the carotid body: from stimulus to response. 1770 92
Despite intensive research, the exact function of
TASK
potassium channels in central and peripheral chemoreception is still under debate. In this study, we investigated the respiration of unrestrained TASK-3 (TASK-3
-/-
) and TASK-1/TASK-3 double knockout (TASK-1/3
-/-
) adult male mice in vivo using a plethysmographic device. Ventilation parameters of TASK-3
-/-
mice were normal under control condition (21% O
2
) and upon hypoxia and hypercapnia they displayed the physiological increase of ventilation. TASK-1/3
-/-
mice showed increased ventilation under control conditions. This increase of ventilation was caused by increased tidal volumes (V
T
), a phenomenon similarly observed in TASK-1
-/-
mice. Under acute hypoxia, TASK-1/3
-/-
mice displayed the physiological increase of the minute volume. Interestingly, this increase was not related to an increase of the respiratory frequency (f
R
), as observed in wild-type mice, but was caused by a strong increase of V
T
. This particular respiratory phenotype is reminiscent of the respiratory phenotype of carotid body-denervated rodents in the compensated state. Acute hypercapnia (5% CO
2
) stimulated ventilation in TASK-1/3
-/-
and wild-type mice to a similar extent; however, at higher CO
2
concentrations (>5% CO
2
) the stimulation of ventilation was more pronounced in TASK-1/3
-/-
mice. At
hyperoxia
(100% O
2
), TASK-1
-/-
, TASK-3
-/-
and wild-type mice showed the physiological small decrease of ventilation. In sharp contrast, TASK-1/3
-/-
mice exhibited an abnormal increase of ventilation under
hyperoxia
. In summary, these measurements showed a grossly normal respiration of TASK-3
-/-
mice and a respiratory phenotype of TASK-1/3
-/-
mice that was characterized by a markedly enhanced tidal volume, similar to the one observed in TASK-1
-/-
mice. The abnormal
hyperoxia
response, exclusively found in TASK-1/3
-/-
double mutant mice, indicates that both TASK-1 and TASK-3 are essential for the
hyperoxia
-induced hypoventilation. The peculiar respiratory phenotype of TASK-1/3 knockout mice is reminiscent of the respiration of animals with long-term carotid body dysfunction. Taken together, TASK-1 and TASK-3 appear to serve specific and distinct roles in the complex processes underlying chemoreception and respiratory control.
...
PMID:Abnormal respiration under hyperoxia in TASK-1/3 potassium channel double knockout mice. 2867 76
