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Query: UMLS:C0037315 (
sleep apnea
)
8,000
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Recent studies revealed that unstable ventilation control is one of mechanisms underlying the occurrence of
sleep apnea
. Thus, we investigated whether
TASK-1
, an acid-sensitive potassium channel, plays a role in the occurrence of
sleep apnea
. First, the expression of
TASK-1
transcriptions on brainstem was checked by in situ hybridization. Then, the correlation between the central apneic episodes and protein contents of
TASK-1
measured by western blot was analyzed from 27 male rats. Results showed that
TASK-1
mRNAs were widely distributed on the putative central chemoreceptors such as locus coeruleus, nucleus tractus solitarius and medullary raphe, etc. Both the total spontaneous apnea index (TSAI) and spontaneous apnea index in NREM sleep (NSAI) were positively correlated with
TASK-1
protein contents (r=0.547 and 0.601, respectively, p<0.01). However, the post-sigh
sleep apnea
index (PAI) had no relationship with
TASK-1
protein. Thus, we concluded that
TASK-1
channels may function as central chemoreceptors that play a role in spontaneous sleep apneas in rats.
...
PMID:Expression of TASK-1 in brainstem and the occurrence of central sleep apnea in rats. 1827 37
In the past year, there have been numerous advances in our understanding of arrhythmia mechanisms, diagnosis, and new therapies. We have seen advances in basic cardiac electrophysiology with data suggesting that secretoneurin may be a biomarker for patients at risk of ventricular arrhythmias, and we have learned of the potential role of an NPR-C (natriuretic peptide receptor-C) in atrial fibrosis and the role of an atrial specific 2-pore potassium channel
TASK-1
as a therapeutic target for atrial fibrillation. We have seen studies demonstrating the role of sensory neurons in
sleep apnea
-related atrial fibrillation and the association between bariatric surgery and atrial fibrillation ablation outcomes. Artificial intelligence applied to electrocardiography has yielded estimates of age, sex, and overall health. We have seen new tools for collection of patient-centered outcomes following catheter ablation. There have been significant advances in the ability to identify ventricular tachycardia termination sites through high-density mapping of deceleration zones. We have learned that right ventricular dysfunction may be a predictor of survival benefit after implantable cardioverter-defibrillator implantation in patients with nonischemic cardiomyopathy. We have seen further insights into the role of His bundle pacing on improving outcomes. As our understanding of cardiac laminopathies advances, we may have new tools to predict arrhythmic event rates in gene carriers. Finally, we have seen numerous advances in the treatment of arrhythmias in patients with congenital heart disease.
...
PMID:Year in Review in Cardiac Electrophysiology. 3242 52
TWIK-related acid-sensitive potassium (
TASK
) channels-members of the two pore domain potassium (K
2P
) channel family-are found in neurons
1
, cardiomyocytes
2-4
and vascular smooth muscle cells
5
, where they are involved in the regulation of heart rate
6
, pulmonary artery tone
5,7
, sleep/wake cycles
8
and responses to volatile anaesthetics
8-11
. K
2P
channels regulate the resting membrane potential, providing background K
+
currents controlled by numerous physiological stimuli
12-15
. Unlike other K
2P
channels,
TASK
channels are able to bind inhibitors with high affinity, exceptional selectivity and very slow compound washout rates. As such, these channels are attractive drug targets, and
TASK-1
inhibitors are currently in clinical trials for obstructive
sleep apnoea
and atrial fibrillation
16
. In general, potassium channels have an intramembrane vestibule with a selectivity filter situated above and a gate with four parallel helices located below; however, the K
2P
channels studied so far all lack a lower gate. Here we present the X-ray crystal structure of
TASK-1
, and show that it contains a lower gate-which we designate as an 'X-gate'-created by interaction of the two crossed C-terminal M4 transmembrane helices at the vestibule entrance. This structure is formed by six residues (
243
VLRFMT
248
) that are essential for responses to volatile anaesthetics
10
, neurotransmitters
13
and G-protein-coupled receptors
13
. Mutations within the X-gate and the surrounding regions markedly affect both the channel-open probability and the activation of the channel by anaesthetics. Structures of
TASK-1
bound to two high-affinity inhibitors show that both compounds bind below the selectivity filter and are trapped in the vestibule by the X-gate, which explains their exceptionally low washout rates. The presence of the X-gate in
TASK
channels explains many aspects of their physiological and pharmacological behaviour, which will be beneficial for the future development and optimization of
TASK
modulators for the treatment of heart, lung and sleep disorders.
...
PMID:A lower X-gate in TASK channels traps inhibitors within the vestibule. 3249 42
