TASK Channels Research Articles

Green Computation Offloading With DRL in Multi‐Access Edge Computing

ABSTRACTIn multi‐access edge computing (MEC), computational task offloading of mobile terminals (MT) is expected to provide the green applications with the restriction of energy consumption and service latency. Nevertheless, the diverse statuses of a range of edge servers and mobile terminals, along with the fluctuating offloading routes, present a challenge in the realm of computational task offloading. In order to bolster green applications, we present an innovative computational task offloading model as our initial approach. In particular, the nascent model is constrained by energy consumption and service latency considerations: (1) Smart mobile terminals with computational capabilities could serve as carriers; (2) The diverse computational and communication capacities of edge servers have the potential to enhance the offloading process; (3) The unpredictable routing paths of mobile terminals and edge servers could result in varied information transmissions. We then propose an improved deep reinforcement learning (DRL) algorithm named PS‐DDPG with the prioritized experience replay (PER) and the stochastic weight averaging (SWA) mechanisms based on deep deterministic policy gradients (DDPG) to seek an optimal offloading mode, saving energy consumption. Next, we introduce an enhanced deep reinforcement learning (DRL) algorithm named PS‐DDPG, incorporating the prioritized experience replay (PER) and stochastic weight averaging (SWA) techniques rooted in deep deterministic policy gradients (DDPG). This approach aims to identify an efficient offloading strategy, thereby reducing energy consumption. Fortunately, algorithm is proposed for each MT, which is responsible for making decisions regarding task partition, channel allocation, and power transmission control. Our developed approach achieves the ultimate estimation of observed values and enhances memory via write operations. The replay buffer holds data from previous time slots to upgrade both the actor and critic networks, followed by a buffer reset. Comprehensive experiments validate the superior performance, including stability and convergence, of our algorithm when juxtaposed with prior studies.

Salidroside ameliorates hypoxic pulmonary hypertension by regulating the two-pore domain potassium TASK-1 channel

BackgroundHypoxic pulmonary vasoconstriction (HPV) is a reflex constriction of vascular smooth muscle. This study aims to investigate the role of Salidroside (Sal) in pulmonary arterial dilatation and the potential mechanism of Sal regulating hypoxic pulmonary hypertension in vitro and in vivo. MethodsA rat model of hypoxic pulmonary hypertension (HPH) was constructed using hypoxic chamber. The effect of Sal on HPH were evaluated using vascular ring, whole cell patch-clamp, WGA staining, HE staining, and Sirius Scarlet staining assays. ResultsSal treatment alleviated the injury of acute hypoxia on pulmonary circulation in SD rats. Meanwhile, Sal treatment reduced the pulmonary vascular tone of acute hypoxia in a concentration-dependent manner, which was involved in the TWIK-related acid-sensitive potassium channel 1 (TASK-1) mediating diastolic effect. We found that Sal treatment significantly increased the TASK-1 current of pulmonary artery smooth muscle cells (PASMCs) in a concentration-dependent manner, as well as reversed the inhibitory effect of acute hypoxia on the TASK-1 current. Moreover, Sal treatment improved the TASK-1 current density, suppressed the proliferation, and enhanced the apoptosis of PASMCs in SD rats under continuous hypoxic condition. In addition, we found that the electrophysiological remodeling and pulmonary vascular remodeling of PASMCs were improved by the treatment of Sal through the regulation of TASK-1 channel. ConclusionsSal could alleviate HPH by restoring the function of TASK-1 channel, which may provide a novel method for the treatment of HPH.

Downregulation of TASK-3 Channel Induces Senescence in Granulosa Cells of Bovine Cystic Ovarian Follicles.

Ovarian cysts are linked to hormone imbalances and altered gene expressions, but the connection between cysts and ion channel expression is understudied. This study explored the role of TWIK-related acid-sensitive K+ (TASK) channels in bovine ovarian cyst formation. The ovarian follicles were split into small (5 to 10 mm in diameter) and large (>25 mm in diameter) groups. Among the measured K+, Na+, and Cl- concentrations in follicular fluid (FF) obtained from small-sized follicles (SFs) and large-sized follicles (LFs), the K+ concentration was significantly lower in LFFF. Quantitative PCR, Western blot, and immunocytochemistry data revealed that TASK-3 expression levels significantly decreased by approximately 50% in LFs and granulosa cells obtained from LFs (LFGCs) compared to the corresponding controls. The TASK-3 protein was localized to the plasma membranes of GCs. The diameters of LFGCs were larger than those of SFGCs. The cell swelling response to exposure to a hypotonic solution (200 mOsm/L) was highly reduced in TASK-3-overexpressing cells compared to vector-transfected cells. TASK-3-knockdown cells showed arrested growth. Senescence markers were detected in LFGCs and TASK-3-knockdown cells. These findings suggest that reduced TASK-3 expression in LFs is associated with the inhibition of GC growth, leading to senescence and cyst formation.

Potassium channel TASK-5 forms functional heterodimers with TASK-1 and TASK-3 to break its silence

TASK-5 (KCNK15) belongs to the acid-sensitive subfamily of two-pore domain potassium (K2P) channels, which includes TASK-1 and TASK-3. TASK-5 stands out as K2P channel for which there is no functional data available, since it was reported in 2001 as non-functional and thus “silent”. Here we show that TASK-5 channels are indeed non-functional as homodimers, but are involved in the formation of functional channel complexes with TASK-1 and TASK-3. TASK-5 negatively modulates the surface expression of TASK channels, while the heteromeric TASK-5-containing channel complexes located at the plasma membrane are characterized by changes in single-channel conductance, Gq-coupled receptor-mediated channel inhibition, and sensitivity to TASK modulators. The unique pharmacology of TASK-1/TASK-5 heterodimers, affected by a common polymorphism in KCNK15, needs to be carefully considered in the future development of drugs targeting TASK channels. Our observations provide an access to study TASK-5 at the functional level, particularly in malignant cancers associated with KCNK15.

The TWIK-related acid sensitive potassium 3 (TASK-3) channel contributes to the different effects of anesthetics on the growth and metastasis of ovarian cancer cells

Different anesthetics exert different effects on the long-term outcomes of various cancers. The TWIK-related acid sensitive potassium 3 (TASK-3) channel is an important target of anesthetics and is upregulated in various cancers. However, the role and underlying mechanism of TASK-3 channel in the effects of anesthetics on ovarian cancer remain unknown. Here, we tested whether the TASK-3 channel contributes to the effects of anesthetics on ovarian cancers. We found that the TASK-3 channel was overexpressed in human ovarian cancer and ovarian cancer cell lines. Clinically relevant concentrations of lidocaine, as a TASK-3 channel inhibitor, exert inhibitory effects on tumor growth and metastasis of ovarian cancer cells in vitro and in vivo, whereas the TASK-3 channel potent activator sevoflurane had protumor effects and propofol had no significant effects on tumor growth and metastasis of ovarian cancer. Knockdown of the TASK-3 channel by TASK-3 shRNA attenuated the effects of lidocaine and sevoflurane. Moreover, mitochondrial TASK-3 channel contributes to the effects of lidocaine and sevoflurane on the mitochondrial functions of ovarian cancer. Taken together, the TASK-3 channel, especially the mitochondrial TASK-3 (MitoTASK-3) channel, is a molecular substrate for the effects of lidocaine and sevoflurane on the tumor growth and metastasis of ovarian cancer.

Nfluence of extracellular acidosis on the functional contribution of KATP and TASK-1 potassium channels to the regulation of vascular tone in early postnatal ontogenesis

The activity of many proteins and, as a result, of the mechanisms of vascular tone regulation depends on pH. A decrease of pH (uncompensated acidosis), usually causes relaxation of blood vessels, which has been studied in sufficient detail for an adult, matured organism. However, the effect of acidosis on the mechanisms of vascular tone regulation in the early postnatal period remains almost completely unexplored. The aim of this work was to study the effect of extracellular metabolic acidosis on the functional contribution of KATP and TASK-1 potassium channels to the regulation of vascular tone in early postnatal period. We modeled extracellular metabolic acidosis (pH 6.8, equimolar replacement of NaHCO3 with NaCl in solution) and studied isometric contractile responses of the saphenous artery in rats aged 3–4 months and rat pups aged 12–15 days. Arterial contraction to the α1-adrenergic agonist methoxamine at pH 6.8 was reduced compared to normal pH 7.4 in both 3–4-month-old and 12–15-day-old rats. The KATP channel blocker glibenclamide did not change the arterial responses to methoxamine, neither at pH 7.4 nor at pH 6.8 in any of the age groups. The TASK-1 channel blocker AVE1231 did not alter arterial contractile responses at any pH in 3–4-month-old rats. However, in 12–15-day-old rat pups, the increase in contractile responses to methoxamine under the influence of AVE1231 was less at pH 6.8 than at pH 7.4. Thus, the results of this work demonstrate that acidosis reduces the contractile activity of the arteries of 3–4-month-old animals and animals during early postnatal ontogenesis, while in the latter, the anticontractile role of TASK-1 channels decreases, and KATP channels do not affect the regulation of vascular tone, either under normal, or at acidic pH in any of the age groups.

Multi-UAV Collaborative Edge Computing Algorithm for Joint Task Offloading and Channel Resource Allocation

Multi-UAV Collaborative Edge Computing Algorithm for Joint Task Offloading and Channel Resource Allocation

ASSESSMENT OF ANGIOTENSIN II-INDUCED CALCIUM SIGNALS IN PRIMARY HUMAN ADRENOCORTICAL CELLS

Objective: Primary aldosteronism (PA), a common form of secondary hypertension, is characterized by an increase of cytosolic intracellular Ca2+ concentrations [Ca2+]i. Our aim is to investigate transients and oscillations of [Ca2+]i in a human model of isolated CD56+ aldosterone-producing adenoma (APA) cells and normal surrounding adrenocortical (NAC) cells. Design and method: We monitored [Ca2+]i, in CD56+ NAC and APA cells in basal condition and after Angiotensin II (Ang II) stimulation using Fura-2 dye and live confocal microscopy, and we developed a custom-made pipeline to analyze calcium signals in terms of frequency and peak parameters like amplitude, full width at half maximum (FWHM) and area under the curve (AUC). To investigate the potential role of the two-pore domain K+ TASK- 2 channel in regulating Ca2+ signals, TASK-2 channels of NAC cells were pharmacologically inhibited using Quinidine (20 microM) 20’ prior to [Ca2+]i imaging acquisition. Results: Resting [Ca2+]i basal levels in NAC (n=11) were higher (0.76 a.u.+- 0.04) than in APA (n=12) (0.56 a.u.+- 0.05, p= 0.0087). NAC TASK-2 inhibition decreased resting [Ca2+]i to 0.58 a.u. +- 0.07 (p > 0.05). Spontaneous Ca2+ activity was higher in NAC with significant higher amplitude and AUC parameters compared to APA cells. Quinidine further increased spontaneous activity in NAC while decreased Amplitude and AUC. For both cell types stimulation with 2 doses of Ang II concentrations [10 -8 and 10 -9 mM], higher Ang II doses promoted higher Ca2+ peak parameters, amplitude and AUC, and a significant decrease in events frequency. Comparison between APA and NAC revealed that, regardless of Ang II dose, first Ca2+ transient parameters are intensified in NAC. However, APA showed consistent elevated subsequent Ca2+ oscillations parameters (Amplitude and AUC), frequency, and degree of oscillation compared to NAC cells stimulated with similar Ang II doses. NAC TASK-2 inhibited cells, when stimulated with [10 -9 mM] Ang II, displayed only increased subsequent peak parameters. Conclusions: The bias-free approach designed to quantitatively assess [Ca2+]i signals, revealed significant differences in [Ca2+]i dynamics of human NAC and APA cells.

Joint optimization of multi-dimensional resource allocation and task offloading for QoE enhancement in Cloud-Edge-End collaboration

Cloud-Edge-End Collaboration (CEEC) computing architecture inherits many merits from both edge computing and cloud computing and thus is considered as a promising candidate for future network services. In CEEC, user’s QoE is impacted by offload performance which should consider offload strategy, computational resources and network status simultaneously. However, previous offload optimization studies neglect the joint consideration of dependent task offloading, computational resources and channel resources, which may not produce potential performance improvement. In this paper, we investigate the joint optimization of dependent task offloading, computational resource allocation, user transmission power control, and channel resource allocation in the CEEC scenario, with the goal of maximizing user’s QoE. Initially, a new QoE metric is defined to capture the impacts of delay and energy consumption on user’s QoE. Following this definition, we formulate the joint optimization problem as a Mixed Integer Nonlinear Programming (MINLP) problem and introduce a method of multi-agent deep reinforcement learning to solve our MINLP problem with high computation complexity. Extensive experiments are performed, and experimental results show that our proposed scheme outperforms baselines in a series of metrics.

A novel TASK channel antagonist nasal spray reduces sleep apnea severity in physiological responders: a randomized, blinded, trial.

Preclinical and human physiological studies indicate that topical, selective TASK 1/3 K+ channel antagonism increases upper airway dilator muscle activity and reduces pharyngeal collapsibility during anesthesia and nasal breathing during sleep. The primary aim of this study was to determine the effects of BAY2586116 nasal spray on obstructive sleep apnea (OSA) severity and whether individual responses vary according to differences in physiological responses and route of breathing. Ten people (5 females) with OSA [apnea-hypopnea index (AHI) = 47 ± 26 events/h (means ± SD)] who completed previous sleep physiology studies with BAY2586116 were invited to return for three polysomnography studies to quantify OSA severity. In random order, participants received either placebo nasal spray (saline), BAY2586116 nasal spray (160 µg), or BAY2586116 nasal spray (160 µg) restricted to nasal breathing (chinstrap or mouth tape). Physiological responders were defined a priori as those who had improved upper airway collapsibility (critical closing pressure ≥2 cmH2O) with BAY2586116 nasal spray (NCT04236440). There was no systematic change in apnea-hypopnea index (AHI3) from placebo versus BAY2586116 with either unrestricted or nasal-only breathing versus placebo (47 ± 26 vs. 43 ± 27 vs. 53 ± 33 events/h, P = 0.15). However, BAY2586116 (unrestricted breathing) reduced OSA severity in physiological responders compared with placebo (e.g., AHI3 = 28 ± 11 vs. 36 ± 12 events/h, P = 0.03 and ODI3 = 18 ± 10 vs. 28 ± 12 events/h, P = 0.02). Morning blood pressure was also lower in physiological responders after BAY2586116 versus placebo (e.g., systolic blood pressure = 137 ± 24 vs. 147 ± 21 mmHg, P < 0.01). In conclusion, BAY2586116 reduces OSA severity during sleep in people who demonstrate physiological improvement in upper airway collapsibility. These findings highlight the therapeutic potential of this novel pharmacotherapy target in selected individuals.NEW & NOTEWORTHY Preclinical findings in pigs and humans indicate that blocking potassium channels in the upper airway with topical nasal application increases pharyngeal dilator muscle activity and reduces upper airway collapsibility. In this study, BAY2586116 nasal spray (potassium channel blocker) reduced sleep apnea severity in those who had physiological improvement in upper airway collapsibility. BAY2586116 lowered the next morning's blood pressure. These findings highlight the potential for this novel therapeutic approach to improve sleep apnea in certain people.

Expression of TASK-1 channel in mouse Leydig cells

Expression of TASK-1 channel in mouse Leydig cells

Unravelling the signaling pathway downstream of the neurokinin receptor in atrium: discovering novel anti-arrhythmic targets for treatment of atrial fibrillation

Abstract Background Stimulation of neurokinin receptor (NKR) 3 is anti-fibrillatory by prolonging the action potential duration (APD) of atrial cardiomyocytes via inhibition of a background potassium current (1). The NKR is a Gq/11 protein-coupled receptor, but the downstream intracellular pathway and the end-effector potassium (K+)-channel in atrium are unknown. We aimed at unravelling the components of this pathway in atrial cardiomyocytes. Methods Rabbit (New Zealand White) atrial cardiomyocytes were isolated from Langendorff-perfused hearts by enzymatic dissociation. Human immortalized atrial myocytes (HiAMs) were developed, and kindly provided by our collaborators (2). Adult human atrial cardiomyocytes were obtained by enzymatic dissociation from left atrial appendages (LAA) routinely removed from atrial fibrillation (AF) patients undergoing minimally invasive surgical pulmonary vein isolation in the clinics. Action potentials (APs) and K+ currents were recorded at 36.5°C with the amphotericin-B-perforated patch clamp technique. RNA was isolated from rabbit atrial tissue and sequenced on an Illumina HiSeq4000 platform. Results In rabbit atrial cardiomyocytes, stimulation of NKR3 prolonged APD by ∼50% and inhibited an background outward K+-current by ∼45%. Inhibition of phosphokinase C (PKC) did not prevent APD prolongation by NKR3 stimulation, but application of a diacylglycerol (DAG) analog inhibited an outward K+-current by ∼40% indicating that DAG, but not PKC, is downstream of NKR3. Inhibition of phosphatidylcholine-specific phospholipase C (PC-PLC), but not of phosphoinositide-specific PLC (PI-PLC), reduced APD increase by NKR3 stimulation by five-fold, indicating PC-PLC as the intracellular signaling molecule. In HiAMs, direct PLC activation prolonged APD by 34%. RNA sequencing analysis revealed potential end-targets of the NKR3 pathway in rabbit. Inhibition of small conductance potassium (KCNN2/KCNN3) or TASK-1 (KCNK3) channels (prolonging APD by ∼15%) did not abolish the APD prolongation effect by subsequent NKR3 stimulation (∼50%), indicating that these channels are not the end-effector K+-channels inhibited by NKR3 stimulation. Inhibition of constitutive KACh channels had little effect on APD at baseline. Nevertheless, APD shortening by agonist-induced KACh channel activity could be completely reversed by NKR3 stimulation, indicating that increased outward KACh current can be fully counterbalanced by the reduction in K+ background current. In human atrial cardiomyocytes from AF patients, stimulation of NKR3 prolonged APD by 25%, Conclusions PC-PLC and DAG, but not PI-PLC and PKC, are intracellularly downstream of NKR3 in atrial rabbit cardiomyocytes. Stimulation of the NKR pathway may have an anti-arrhythmic potential in patients with AF.

The transcription factor ETV1 regulates expression of the atrial specific potassium channel TASK-1 and modulates cardiac action potentials

Abstract Background In recent years, the two-pore domain potassium channel TASK-1 has been identified to play an important role in the pathophysiology of atrial fibrillation (AF). In cardiac tissue, TASK-1 is almost exclusively expressed in the atria and significantly upregulated in AF patients. Moreover, it has been characterized as a key player in action potential (AP) shortening observed during AF, making it a promising target for antiarrhythmic therapy. However, the underlying transcriptional mechanisms responsible for TASK-1 upregulation during AF are still unclear. A few years ago, the transcription factor ETV1 has been described to induce atrial remodeling and arrhythmia. Similar to TASK-1, ETV1 is predominantly expressed in the atria and upregulated in AF patients. Therefore, investigating possible interactions between ETV1 and TASK-1 is crucial to further understand atrial remodeling and develop new antiarrhythmic strategies. Purpose The purpose of this study was to investigate the effects of ETV1 regulation on TASK-1 expression. For that, electrophysiological effects of ETV1 modulation on TASK-1 currents and action potential formation were studied on HL-1 cardiomyocytes. Methods ETV1 modulation was achieved either through application of the pharmacological ETV1-inhibitor BRD32048 (1 µM) or transfection of HL-1 cells with a specific ETV1-siRNA. Electrophysiological effects of ETV1 inhibition were assessed using two-electrode voltage clamp experiments on Xenopus laevis oocytes heterologously expressing TASK-1 as well as whole-cell patch clamp measurements on HL-1 cells after pharmacological- and siRNA-mediated ETV1 inhibition. Chromatin immunoprecipitation combined with real-time qPCR (ChIP-qPCR) and ATAC-seq experiments were performed to identify the epigenetic interaction between ETV1 and the KCNK3 gene encoding TASK-1. Results TASK-1 currents were markedly reduced in Xenopus laevis oocytes after inhibition of ETV1. Furthermore, both pharmacological inhibition and siRNA-mediated knockdown of ETV1 caused a significant decrease of TASK-1 currents in HL-1 cells by 35.8% and 39.3%, respectively. These effects were associated with a statistically significant prolongation of the action potential duration at 90% repolarization (APD90) by 28.5% after functional inhibition and 24.9% after siRNA-knockdown. This correlated with a significant decrease of TASK-1 expression on mRNA and protein level. In addition, ATAC-seq data and ChIP-qPCR revealed an enrichment of ETV1 binding within accessible regulatory elements at the KCNK3 gene locus. Conclusions ETV1-knockdown shows strong inhibitory effects on TASK-1 while ChIP-qPCR and ATAC-seq data suggest that ETV1 acts as a direct transcriptional activator of KCNK3. The finding that ETV1 is involved in the regulation of TASK-1 improves our understanding of the pathomechanisms underlying AF and will hopefully help to advance TASK-1-based AF therapy.

Activation of neurokinin-III receptors modulates human atrial TASK-1 currents

RationaleThe neurokinin-III receptor was recently shown to regulate atrial cardiomyocyte excitability by inhibiting atrial background potassium currents. TASK-1 (hK2P3.1) two-pore-domain potassium channels, which are expressed atrial-specifically in the human heart, contribute significantly to atrial background potassium currents. As TASK-1 channels are regulated by a variety of intracellular signalling cascades, they represent a promising candidate for mediating the electrophysiological effects of the Gq-coupled neurokinin-III receptor. ObjectiveTo investigate whether TASK-1 channels mediate the neurokinin-III receptor activation induced effects on atrial electrophysiology. Methods and resultsIn Xenopus laevis oocytes, heterologously expressing neurokinin-III receptor and TASK-1, administration of the endogenous neurokinin-III receptor ligands substance P or neurokinin B resulted in a strong TASK-1 current inhibition. This could be reproduced by application of the high affinity neurokinin-III receptor agonist senktide. Moreover, preincubation with the neurokinin-III receptor antagonist osanetant blunted the effect of senktide. Mutagenesis studies employing TASK-1 channel constructs which lack either protein kinase C (PKC) phosphorylation sites or the domain which is regulating the diacyl glycerol (DAG) sensitivity domain of TASK-1 revealed a protein kinase C independent mechanism of TASK-1 current inhibition: upon neurokinin-III receptor activation TASK-1 channels are blocked in a DAG-dependent fashion. Finally, effects of senktide on atrial TASK-1 currents could be reproduced in patch-clamp measurements, performed on isolated human atrial cardiomyocytes. ConclusionsHeterologously expressed human TASK-1 channels are inhibited by neurokinin-III receptor activation in a DAG dependent fashion. Patch-clamp measurements, performed on human atrial cardiomyocytes suggest that the atrial-specific effects of neurokinin-III receptor activation on cardiac excitability are predominantly mediated via TASK-1 currents.

Lyapunov optimized energy-efficient dynamic offloading with queue length constraints

With the advent of the Internet of Things (IoT), more computation-intensive applications are migrated to IoT devices. Whereas the battery with limited capacity and the processor with low computing power become the bottlenecks that limit its further development. Mobile edge computing (MEC) provides a promising solution to break through the bottlenecks. Many effective methods are proposed to guide how to offload tasks from IoT devices to MEC to enhance the computing capacity and prolong the battery life of devices. This paper investigates the task offloading problem for a multi-device single-MEC system whose status, such as task arrival rate and channel state, is dynamically changing over time and aims at minimizing the energy consumption of devices and maintaining the system stability in the long term. This problem requires lots of future information about the system, which brings a challenge since it is difficult to obtain future information. Moreover, to improve the system performance with respect to task response time, we define an individual queue length threshold for each IoT device such that the queue length of each device can stabilize around the predefined threshold. To address this problem, we first construct a virtual queue for each device to transform the queue length threshold constraint into the virtual queue stability constraint. Secondly, applying the Lyapunov optimization method, the original problem, which requires future system information, is transformed into a problem that only depends on the information of the current time. Thirdly, a dynamic energy-efficient task offloading algorithm is proposed to optimize the time-average energy consumption while maintaining the queue length constraint. This algorithm generates the offloading decision in real-time without requiring system statistical information. Lastly, simulations are conducted to analyze the effect of different parameters on performance. A group of comparisons are given, showing that the task queue length under the proposed method can be controlled effectively compared with the existing studies.

Joint Task Allocation and Resource Optimization Based on an Integrated Radar and Communication Multi-UAV System

This paper investigates the joint task allocation and resource optimization problem in an integrated radar and communication multi-UAV (IRCU) system. Specifically, we assign reconnaissance UAVs and communication UAVs to perform the detection, tracking and communication tasks under the resource, priority and timing constraints by optimizing task allocation, power as well as channel bandwidth. Due to complex coupling among task allocation and resource optimization, the considered problem is proved to be non-convex. To solve the considered problem, we present a loop iterative optimization (LIO) algorithm to obtain the optimal solution. In fact, the mentioned problem is decomposed into three sub-problems, such as task allocation, power optimization and channel bandwidth optimization. At the same time, these three problems are solved by the divide-and-conquer algorithm, the successive convex approximation (SCA) algorithm and the improved particle swarm optimization (PSO) algorithm, respectively. Finally, numerical simulations demonstrate that the proposed LIO algorithm consumes fewer iterations or achieves higher maximum joint performance than other baseline schemes for solving the considered problem.

TWIK-related acid-sensitive potassium channels TASK-1 and TASK-3 may participate in the process of the coexistence of asthma and OSA.

To investigate the role of TWIK-related acid-sensitive potassium channels TASK-1 and TASK-3 in the mechanism of asthma combined with obstructive sleep apnea (OSA) in mice. C57BL/6 mice were randomly divided into four groups: control group (NS-RA), asthma group (OVA-RA), OSA group (NS-IH), and asthma combined with OSA group (OVA-IH). After monitoring lung function in each group, the expression levels of TASK-1 and TASK-3 mRNA and protein in lung tissues were measured, and the correlation between the changes of both and lung function was analyzed. A total of 64 male mice were studied. Penh, serum IgE concentrations, and the percentage of eosinophils in bronchoalveolar lavage fluid (BALF) were higher in OVA-RA and OVA-IH mice compared with NS-RA (P < 0.05),while the above indexes were slightly elevated in NS-IH mice compared with NS-RA (P > 0.05), where the Penh and the percentage of eosinophils in BALF was higher in OVA-IH mice than NS-IH (P < 0.05).Increased TASK-3 mRNA expression (P < 0.05) as well as TASK-1 and TASK-3 protein expression (P > 0.05) in lung tissues of OVA-RA and NS-IH mice compared with NS-RA, and TASK-3 mRNA expression was slightly more in the OVA-IH group compared with NS-RA (P > 0.05), but less compared with OVA-RA (P < 0.05) or NS-IH (P > 0.05), while TASK-1 and TASK-3 protein expression was increased in the OVA-IH group compared with the remaining three groups, and TASK-3 protein expression was associated with lung function impairment was positively correlated with the degree of lung function impairment (P < 0.05). Task-1 and Task-3 may be involved in the pathogenesis of asthma with OSA by affecting lung function.

Exploring the involvement of TASK-1 in the control of isolated rat right atrium function from healthy animals and an experimental model of monocrotaline-induced pulmonary hypertension.

The TASK-1 channel belongs to the two-pore domain potassium channel family. It is expressed in several cells of the heart, including the right atrial (RA) cardiomyocytes and the sinus node, and TASK-1 channel has been implicated in the pathogenesis of atrial arrhythmias (AA). Thus, using the rat model of monocrotaline-induced pulmonary hypertension (MCT-PH), we explored the involvement of TASK-1 in AA. Four-week-old male Wistar rats were injected with 50 mg/kg of MCT to induce MCT-PH and isolated RA function was studied 14 days later. Additionally, isolated RA from six-week-old male Wistar rats were used to explore the ability of ML365, a selective blocker of TASK-1, to modulate RA function. The hearts developed right atrial and ventricular hypertrophy, inflammatory infiltrate and the surface ECG demonstrated increased P wave duration and QT interval, which are markers of MCT-PH. The isolated RA from the MCT animals showed enhanced chronotropism, faster contraction and relaxation kinetics, and a higher sensibility to extracellular acidification. However, the addition of ML365 to extracellular media was not able to restore the phenotype. Using a burst pacing protocol, the RA from MCT animals were more susceptible to develop AA, and simultaneous administration of carbachol and ML365 enhanced AA, suggesting the involvement of TASK-1 in AA induced by MCT. TASK-1 does not play a key role in the chronotropism and inotropism of healthy and diseased RA; however, it may play a role in AA in the MCT-PH model.

Molecular profiling of CO2/pH-sensitive neurons in the locus coeruleus of bullfrogs reveals overlapping noradrenergic and glutamatergic cell identity

Locus coeruleus (LC) neurons regulate breathing by sensing CO2/pH. Neurons within the vertebrate LC are the main source of norepinephrine within the brain. However, they also use glutamate and GABA for fast neurotransmission. Although the amphibian LC is recognized as a site involved in central chemoreception for the control of breathing, the neurotransmitter phenotype of these neurons is unknown. To address this question, we combined electrophysiology and single-cell quantitative PCR to detect mRNA transcripts that define norepinephrinergic, glutamatergic, and GABAergic phenotypes in LC neurons activated by hypercapnic acidosis (HA) in American bullfrogs. Most LC neurons activated by HA had overlapping expression of noradrenergic and glutamatergic markers but did not show strong support for GABAergic transmission. Genes that encode the pH-sensitive K+ channel, TASK2, and acid-sensing cation channel, ASIC2, were most abundant, while Kir5.1 was present in 1/3 of LC neurons. The abundance of transcripts related to norepinephrine biosynthesis linearly correlated with those involved in pH sensing. These results suggest that noradrenergic neurons in the amphibian LC also use glutamate as a neurotransmitter and that CO2/pH sensitivity may be linkedto the noradrenergic cell identity.

Metabolic regulation of the two-pore domain potassium channel TASK-1

TASK-1 is a two-pore potassium ion channel and implicated in the maintenance of cell membrane potential. Little is known about the traffic regulation of TASK-1 under metabolic stress. The present study was designed to explore whether cell surface expression of TASK-1 is modulated by hypoxia. The trafficking of recombinant TASK-1 channels was studied in HEK293T cells under hypoxia induced by sodium cyanide (NaCN). Incubation of cells with NaCN significantly reduced TASK-1 fluorescence intensity at cell periphery, and this effect was inhibited by pretreatment with bisindolylmaleimide (BIM), a specific protein kinase C (PKC) inhibitor. Similar results were confirmed by quantifying extracellular HA-tagged TASK-1 on the cell surface using chemiluminescence assay. NaCN-induced reduction in TASK-1 at cell periphery was also prevented by co-expressing the dominant-negative dynamin 1 (K44E), or cholesterol depletion with MβCD, indicating a potential role of cholesterol and dynamin-dependent endocytosis in PKC-mediated reduction of cell surface TASK-1 by NaCN. Mutagenesis studies further showed that NaCN-induced reduction of TASK-1 at cell periphery was observed in cells expressing wild-type TASK-1 but not mutant TASK-1 with mutation of the dileucine motif (263-264 LL-AA) or the PKC phosphorylation consensus site (T400A). Moreover, Western blot analysis demonstrated that NaCN reduced the amount of wild-type TASK-1 but not the TASK-1 mutants (263-264 LL-AA and T400A) in the membrane fraction. In conclusion, our results demonstrate that cell surface TASK-1 channels are downregulated under metabolic inhibition, possibly through PKC-mediated endocytosis in a cholesterol and dynamin-dependent manner. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.