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Query: UMLS:C0020440 (
hypercapnia
)
7,939
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Acid-sensitive K+ channels of the tandem P-domain K+-channel family (TASK-1 and
TASK-3
) have been implicated in peripheral and central respiratory chemosensitivity; however, because of the lack of decisive pharmacological agents, the final proof of the role of the TASK channel in the chemosensory control of breathing has been missing. In the mouse, TASK-1 and
TASK-3
channels are dispensable for central respiratory chemosensitivity (Mulkey et al., 2007). Here, we have used knock-out animals to determine whether TASK-1 and
TASK-3
channels play a role in the carotid body function and chemosensory control of breathing exerted by the carotid body chemoreceptors. Ventilatory responses to hypoxia (10% O2 in inspired air) and moderate normoxic
hypercapnia
(3-6% CO2 in inspired air) were significantly reduced in TASK-1 knock-out mice. In contrast,
TASK-3
-deficient mice showed responses to both stimuli that were similar to those developed by their wild-type counterparts. TASK-1 channel deficiency resulted in a marked reduction of the hypoxia (by 49%)- and CO2 (by 68%)-evoked increases in the carotid sinus nerve chemoafferent discharge recorded in the in vitro superfused carotid body/carotid sinus nerve preparations. Deficiency in both TASK-1 and
TASK-3
channels increased baseline chemoafferent activity but did not cause a further reduction of the carotid body chemosensory responses. These observations provide direct evidence that TASK-1 channels contribute significantly to the increases in the carotid body chemoafferent discharge in response to a decrease in arterial P(O2) or an increase in P(CO2)/[H+]. TASK-1 channels therefore play a key role in the control of ventilation by peripheral chemoreceptors.
...
PMID:A role for TASK-1 (KCNK3) channels in the chemosensory control of breathing. 1875 86
Background K(+) channels of the TASK family are believed to participate in sensory transduction by chemoreceptor (glomus) cells of the carotid body (CB). However, studies on the systemic CB-mediated ventilatory response to hypoxia and
hypercapnia
in TASK1- and/or
TASK3
-deficient mice have yielded conflicting results. We have characterized the glomus cell phenotype of TASK-null mice and studied the responses of individual cells to hypoxia and other chemical stimuli. CB morphology and glomus cell size were normal in wild-type as well as in TASK1(-/-) or double TASK1/3(-/-) mice. Patch-clamped TASK1/3-null glomus cells had significantly higher membrane resistance and less hyperpolarized resting potential than their wild-type counterpart. These electrical parameters were practically normal in TASK1(-/-) cells. Sensitivity of background currents to changes of extracellular pH was drastically diminished in TASK1/3-null cells. In contrast with these observations, responsiveness to hypoxia or
hypercapnia
of either TASK1(-/-) or double TASK1/3(-/-) cells, as estimated by the amperometric measurement of catecholamine release, was apparently normal. TASK1/3 knockout cells showed an enhanced secretory rate in basal (normoxic) conditions compatible with their increased excitability. Responsiveness to hypoxia of TASK1/3-null cells was maintained after pharmacological blockade of maxi-K(+) channels. These data in the TASK-null mouse model indicate that
TASK3
channels contribute to the background K(+) current in glomus cells and to their sensitivity to external pH. They also suggest that, although TASK1 channels might be dispensable for O(2)/CO(2) sensing in mouse CB cells,
TASK3
channels (or TASK1/3 heteromers) could mediate hypoxic depolarization of normal glomus cells. The ability of TASK1/3(-/-) glomus cells to maintain a powerful response to hypoxia even after blockade of maxi-K(+) channels, suggests the existence of multiple sensor and/or effector mechanisms, which could confer upon the cells a high adaptability to maintain their chemosensory function.
...
PMID:Carotid body chemosensory responses in mice deficient of TASK channels. 2035 Oct 62
Serotonin (5-hydroxytryptamine, 5-HT) neurons are widely considered to play an important role in central respiratory chemoreception. Although many studies in the past decades have supported this hypothesis, there had been concerns about its validity until recently. One recurring claim had been that 5-HT neurons are not consistently sensitive to
hypercapnia
in vivo. Another belief was that 5-HT neurons do not stimulate breathing; instead, they inhibit or modulate respiratory output. It was also believed by some that 5-HT neuron chemosensitivity is dependent on TASK channels, but mice with genetic deletion of TASK-1 and
TASK-3
have a normal hypercapnic ventilatory response. This review explains why these principal arguments against the hypothesis are not supported by existing data. Despite repeated challenges, a large body of evidence now supports the conclusion that at least a subset of 5-HT neurons are central chemoreceptors.
...
PMID:Serotonin neurons and central respiratory chemoreception: where are we now? 2474 50
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
Leptin is an adipose-derived hormone that plays an important role in the regulation of breathing. It has been demonstrated that obesity-related hypoventilation or apnea is closely associated with leptin signaling pathways. Perturbations of leptin signaling probably contribute to the reduced sensitivity of respiratory chemoreceptors to hypoxia/
hypercapnia
. However, the underlying mechanism remains incompletely understood. The present study is to test the hypothesis that leptin signaling contributes to modulating a hypoxic ventilatory response. The respiratory function was assessed in conscious obese Zucker rats or lean littermates treated with an injection of leptin. During exposure to hypoxia, the change in minute ventilation was lower in obese Zucker rats than chow-fed lean littermates or high fat diet-fed littermates. Such a change was abolished in all groups after carotid body denervation. In addition, the expression of phosphorylated signal transducers and activators of transcription 3 (pSTAT3), as well as putative O
2
-sensitive K
+
channels including TASK-1,
TASK-3
and TASK-2 in the carotid body, was significantly reduced in obese Zucker rats compared with the other two phenotype littermates. Chronic administration of leptin in chow-fed lean Zucker rats failed to alter basal ventilation but vigorously increased tidal volume, respiratory frequency, and therefore minute volume during exposure to hypoxia. Likewise, carotid body denervation abolished such an effect. In addition, systemic leptin elicited enhanced expression of pSTAT3 and TASK channels. In conclusion, these data demonstrate that leptin signaling facilitates hypoxic ventilatory responses probably through upregulation of pSTAT3 and TASK channels in the carotid body. These findings may help to better understand the pathogenic mechanism of obesity-related hypoventilation or apnea.
...
PMID:Leptin Signaling in the Carotid Body Regulates a Hypoxic Ventilatory Response Through Altering TASK Channel Expression. 2963 98
