Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that there are few clinical drugs that can improve the pathology these diseases by acting on potassium or calcium ions. Although a few novel ion-channelspecific modulators have been discovered, meaningful therapies have largely not yet been realized. The lack of target-specific drugs, their requirement to cross the blood–brain barrier, and their exact underlying mechanisms all need further attention. This review aims to explain the urgent problems that need research progress and provide comprehensive information aiming to arouse the research community's interest in the development of ion channel-targeting drugs and the identification of new therapeutic targets for that can increase the cure rate of nervous system diseases and reduce the occurrence of adverse reactions in other systems.

Intermediate conductance, Ca^2＋-activated K^＋ channels： a novel target for chronic renal diseases

Renal failure is a medical condition in which the kidneys are not working properly. There are two types of kidney failure： 1） acute kidney failure, which is sudden and often reversible with adequate treatment; and 2） chronic renal failure, which develops slowly and often is not reversible. The last stage of chronic renal failure is fatal without dialysis or kidney transplant. The treatment for chronic renal failure is focusing on slowing the progression of kidney damage. Several reports have described a promising approach to slow the loss of renal function through inhibition of the basolateral membrane, Ca^2＋-activated K^＋ （KCa3.1） channel with a selective and nontoxic blocker TRAM-34. This review summarizes pathophysiological studies that describe the role of KCa3.1 in kidney diseases.

Arsenic exposure decreases rhythmic contractions of vascular tone through sodium transporters and K^+ channels

Arsenic-contaminated drinking water is a public health problem in countries such as Taiwan, Bangladesh, United States, Mexico, Argentina, and Chile. The chronic ingestion of arsenic-contaminated drinking water increases the risk for ischemic heart disease, cerebrovascular disease, and prevalence of hypertension. Although toxic arsenic effects are controversial, there is evidence that a high concentration of arsenic may induce hypertension through increase in vascular tone and resistance. Vascular tone is regulated by the rhythmic contractions of the blood vessels, generated by calcium oscillations in the cytosol of vascular smooth muscle cells. To regulate the cytosolic calcium oscillations, the membrane oscillator model involves the participation of Ca2+ channels, calcium-activated K+ channels, Na+/Ca2+exchange, plasma membrane Ca2+-ATPase, and the Na+/K+-ATPase. However, little is known about the role of K+ uptake by sodium transporters [Na+/K+-ATPase or Na+-K+-2Cl-(NKCC1)] on the rhythmic contractions.Vascular rhythmic contractions, or vasomotion are a local mechanism to regulate vascular resistance andblood flow. Since vascular rhythmic contractions of blood vessels are involved in modulating the vascular resistance, the blood flow, and the systemic pressure,we suggest a model explaining the participation of the sodium pump and NKCC1 co-transporter in low dose arsenic exposure effects on vasomotion and vascular dysfunction.

Lithium-Ion Charged Polymer Channels Flattening Lithium Metal Anode

The concentration difference in the near-surface region of lithium metal is the main cause of lithium dendrite growth.Resolving this issue will be key to achieving high-performance lithium metal batteries(LMBs).Herein,we construct a lithium nitrate(LiNO_(3))-implanted electroactiveβphase polyvinylidene fluoride-co-hexafluoropropylene(PVDF-HFP)crystalline polymorph layer(PHL).The electronegatively charged polymer chains attain lithium ions on the surface to form lithium-ion charged channels.These channels act as reservoirs to sustainably release Li ions to recompense the ionic flux of electrolytes,decreasing the growth of lithium dendrites.The stretched molecular channels can also accelerate the transport of Li ions.The combined effects enable a high Coulombic efficiency of 97.0%for 250 cycles in lithium(Li)||copper(Cu)cell and a stable symmetric plating/stripping behavior over 2000 h at 3 mA cm^(-2)with ultrahigh Li utilization of 50%.Furthermore,the full cell coupled with PHL-Cu@Li anode and Li Fe PO_(4) cathode exhibits long-term cycle stability with high-capacity retention of 95.9%after 900 cycles.Impressively,the full cell paired with LiNi_(0.87)Co_(0.1)Mn_(0.03)O_(2)maintains a discharge capacity of 170.0 mAh g^(-1)with a capacity retention of 84.3%after 100 cycles even under harsh condition of ultralow N/P ratio of 0.83.This facile strategy will widen the potential application of LiNO_(3)in ester-based electrolyte for practical high-voltage LMBs.

Transient receptor potential channels as predictive marker and potential indicator of chemoresistance in colon cancer

Transient receptor potential(TRP)channels are strongly associated with colon cancer development and progression.This study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature,with further validation of signature in real world samples from our hospital treated patient samples.Kaplan-Meier(K-M)survival analysis and receiver operating characteristic(ROC)curves were employed to evaluate this gene signature’s predictive accuracy and robustness in both training and testing cohorts,respectively.Additionally,the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature’s immune infiltration landscape and underlying functional implications.The support vector machine algorithm was applied to evaluate the signature’s potential in predicting chemotherapy outcomes.The findings unveiled a novel three TRP channels-related gene signature(MCOLN1,TRPM5,and TRPV4)in colon adenocarcinoma(COAD).The ROC and K-M survival curves in the training dataset(AUC=0.761;p=1.58e-05)and testing dataset(AUC=0.699;p=0.004)showed the signature’s robust predictive capability for the overall survival of COAD patients.Analysis of the immune infiltration landscape associated with the signature revealed higher immune infiltration,especially an increased presence of M2 macrophages,in high-risk group patients compared to their low-risk counterparts.High-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy,evident through increased CD86 and PD-1 expression profiles.Moreover,the TRPM5 gene within the signature was highly expressed in the chemoresistance group(p=0.00095)and associated with poor prognosis(p=0.036)in COAD patients,highlighting its role as a hub gene of chemoresistance.Ultimately,this signature emerged as an independent prognosis factor for COAD patients(p=6.48e-06)and expression of model gene are validated by public data and real-world patients.Overall,this bioinformatics study provides valuable insights into the prognostic implications and potential chemotherapy resistance mechanisms associated with TRPs-related genes in colon cancer.

Involvement of leak K^+ channels in neurological disorders

TWIK-related acid-sensitive K+(TASK) channels give rise to leak K+ currents which influence the resting membrane potential and input resistance. The wide expression of TASK1 and TASK3 channels in the central nervous system suggests that these channels are critically involved in neurological disorders. It has become apparent in the past decade that TASK channels play critical roles for the development of various neurological disorders. In this review, I describe evidence for their roles in ischemia, epilepsy, learning/memory/cognition and apoptosis.

Inhibitory Effects of Blockage of Intermediate Conductance Ca^(2+) -Activated K^+ Channels on Proliferation of Hepatocellular Carcinoma Cells

The roles of intermediate conductance Ca2＋-activated K＋ channel （IKCal） in the pathogene- sis of hepatocellular carcinoma （HCC） were investigated. Immunohistochemistry and Western blotting were used to detect the expression of IKCal protein in 50 HCC and 20 para-carcinoma tissue samples. Real-time PCR was used to detect the transcription level of IKCal mRNA in 13 HCC and 11 para-carcinoma tissue samples. The MTT assay was used to measure the function of IKCal in human HCC cell line HepG2 in vitro. TRAM-34, a specific blocker of IKCal, was used to intervene with the function of IKCal. As compared with para-carcinoma tissue, an over-expression of IKCal protein was detected in HCC tissue samples （P〈0.05）. The mRNA expression level of IKCal in HCC tissues was 2.17 times higher than that in para-carcinoma tissues. The proliferation of HepG2 cells was suppressed by TRAM-34 （0.5, 1.0, 2.0 and 4.0 pxnol/L） in vitro （P〈0.05）. Our results suggested that IKCal may play a role in the proliferation of human HCC, and IKCal blockers may represent a potential therapeutic strategy for HCC.

Influence of pore structure heterogeneity on channeling channels during hot water flooding in heavy oil reservoir based on CT scanning

Hot water flooding is an effective way to develop heavy oil reservoirs.However,local channeling channels may form,possibly leading to a low thermal utilization efficiency and high water cut in the reservoir.The pore structure heterogeneity is an important factor in forming these channels.This study proposes a method that mixes quartz sand with different particle sizes to prepare weakly heterogeneous and strongly heterogeneous models through which hot water flooding experiments are conducted.During the experiments,computer tomography(CT)scanning identifies the pore structure and micro remaining oil saturation distribution to analyze the influence of the pore structure heterogeneity on the channeling channels.The oil saturation reduction and average pore size are divided into three levels to quantitatively describe the relationship between the channeling channel distribution and pore structure heterogeneity.The zone where oil saturation reduction exceeds 20%is defined as a channeling channel.The scanning area is divided into 180 equally sized zones based on the CT scanning images,and threedimensional(3D)distributions of the channeling channels are developed.Four micro remaining oil distribution patterns are proposed,and the morphology characteristics of micro remaining oil inside and outside the channeling channels are analyzed.The results show that hot water flooding is more balanced in the weakly heterogeneous model,and the oil saturation decreases by more than 20%in most zones without narrow channeling channels forming.In the strongly heterogeneous model,hot water flooding is unbalanced,and three narrow channeling channels of different lengths form.In the weakly heterogeneous model,the oil saturation reduction is greater in zones with larger pores.The distribution range of the average pore size is larger in the strongly heterogeneous model.The network remaining oil inside the channeling channels is less than outside the channeling channels,and the hot water converts the network remaining oil into cluster,film,and droplet remaining oil.

K^+channels inhibited by hydrogen peroxide mediate abscisic acid signaling in Vicia guard cells

A number of studies show that environmental stress conditions increase abscisic acid (ABA) and hydrogen peroxide (H2O2) levels in plant cells. Despite this central role of ABA in altering stomatal aperture by regulating guard cell ion transport, little is known concerning the relationship between ABA and H2O2 in signal transduction leading to stomatal movement. Epidermal strip bioassay illustrated that ABA- inhibited stomatal opening and ABA-induced stomatal closure were abolished partly by externally added catalase (CAT) or diphenylene iodonium (DPl), which are a H2O2 scavenger and a NADPH oxidase inhibitor respectively. In contrast, internally added CAT or DPI nearly completely or partly reversed ABA-induced closure in half-stoma. Consistent with these results, whole-cell patch-clamp analysis showed that intracellular application of CAT or DPI partly abolished ABA-inhibited inward K+ current across the plasma membrane of guard cells. H2O2 mimicked ABA to inhibit inward K+ current, an effect which was reversed by the addition of ascorbic acid (Vc) in patch clamping micropipettes. These results suggested that H2O2 mediated ABA-induced stomatal movement by targeting inward K+ channels at plasma membrane.

Multi-User Semantic Fusion for Semantic Communications over Degraded Broadcast Channels

Degraded broadcast channels(DBC) are a typical multiuser communication scenario, Semantic communications over DBC still lack in-depth research. In this paper, we design a semantic communications approach based on multi-user semantic fusion for wireless image transmission over DBC. The transmitter extracts semantic features for two users separately and then effectively fuses them for broadcasting by leveraging semantic similarity. Unlike traditional allocation of time, power, or bandwidth, the semantic fusion scheme can dynamically control the weight of the semantic features of the two users to balance their performance. Considering the different channel state information(CSI) of both users over DBC,a DBC-Aware method is developed that embeds the CSI of both users into the joint source-channel coding encoder and fusion module to adapt to the channel.Experimental results show that the proposed system outperforms the traditional broadcasting schemes.

Voltage-gated K^+channels promote BT-474 breast cancer cell migration

Objective: A variety of ion channels have been implicated in breast cancer proliferation and metastasis.Voltagegated K+(Kv) channels not only cause repolarization in excitable cells,but are also involved in multiple cellular functions in non-excitable cells.In this study we investigated the role of Kv channels in migration of BT474 breast cancer cells.Methods: Transwell technique was used to separate migratory cells from non-migratory ones and these two groups of cells were subject to electrophysiological examinations and microfluorimetric measurements for cytosolic Ca.Cell migration was examined in the absence or presence of Kv channel blockers.Results: When compared with non-migratory cells,migratory cells had much higher Kv current densities,but rather unexpectedly,more depolarized membrane potential and reduced Cainflux.Reverse transcriptasepolymerase chain reaction(RT-PCR) analysis revealed the presence of Kv1.1,Kv1.3,Kv1.5,Kv2.1,Kv3.3,Kv3.4 and Kv4.3 channels.Cell migration was markedly inhibited by tetraethylammonium(TEA),a delayed rectifier Kv channel blocker,but not by 4-aminopyridine,an A-type Kv channel blocker.Conclusions: Taken together,our results show that increased Kv channel expression played a role in BT474 cell migration,and Kv channels could be considered as biomarkers or potential therapeutic targets for breast cancer metastasis.The mechanism(s) by which Kv channels enhanced migration appeared unrelated to membrane hyperpolarization and Cainflux.

Cooperative Covert Communication in Multi-Antenna Broadcast Channels

With the gradual popularization of 5G communications,the application of multi-antenna broadcasting technology has become widespread.Therefore,this study aims to investigate the wireless covert communication in the two-user cooperative multi-antenna broadcast channel.We focus on the issue that the deteriorated reliability and undetectability are mainly affected by the transmission power.To tackle this issue,we design a scheme based on beamforming to increase the reliability and undetectability of wireless covert communication in the multi-antenna broadcast channel.We first modeled and analyzed the cooperative multi-antenna broadcasting system,and put forward the target question.Then we use the SCA(successive convex approximation)algorithm to transform the target problem into a series of convex subproblems.Then the convex problems are solved and the covert channel capacity is calculated.In order to verify the effectiveness of the scheme,we conducted simulation verification.The simulation results show that the proposed beamforming scheme can effectively improve the reliability and undetectability of covert communication in multi-antenna broadcast channels.

A Deep Learning Based Broadcast Approach for Image Semantic Communication over Fading Channels

We consider an image semantic communication system in a time-varying fading Gaussian MIMO channel,with a finite number of channel states.A deep learning-aided broadcast approach scheme is proposed to benefit the adaptive semantic transmission in terms of different channel states.We combine the classic broadcast approach with the image transformer to implement this adaptive joint source and channel coding(JSCC)scheme.Specifically,we utilize the neural network(NN)to jointly optimize the hierarchical image compression and superposition code mapping within this scheme.The learned transformers and codebooks allow recovering of the image with an adaptive quality and low error rate at the receiver side,in each channel state.The simulation results exhibit our proposed scheme can dynamically adapt the coding to the current channel state and outperform some existing intelligent schemes with the fixed coding block.

Dilation,discrimination and Uhlmann's theorem of link products of quantum channels

We establish the Stinespring dilation theorem of the link product of quantum channels in two different ways,discuss the discrimination of quantum channels,and show that the distinguishability can be improved by self-linking each quantum channel n times as n grows.We also find that the maximum value of Uhlmann's theorem can be achieved for diagonal channels.

Cooperative activation of sodium channels for downgrading the energy efficiency in neuronal information processing

The Hodgkin–Huxley model assumes independent ion channel activation,although mutual interactions are common in biological systems.This raises the problem why neurons would favor independent over cooperative channel activation.In this study,we evaluate how cooperative activation of sodium channels affects the neuron’s information processing and energy consumption.Simulations of the stochastic Hodgkin–Huxley model with cooperative activation of sodium channels show that,while cooperative activation enhances neuronal information processing capacity,it greatly increases the neuron’s energy consumption.As a result,cooperative activation of sodium channel degrades the energy efficiency for neuronal information processing.This discovery improves our understanding of the design principles for neural systems,and may provide insights into future designs of the neuromorphic computing devices as well as systematic understanding of pathological mechanisms for neural diseases.

Effective Capacity of URLLC over Parallel Fading Channels with Imperfect Channel State Information

This paper investigates the effective capacity of a point-to-point ultra-reliable low latency communication(URLLC)transmission over multiple parallel sub-channels at finite blocklength(FBL)with imperfect channel state information(CSI).Based on reasonable assumptions and approximations,we derive the effective capacity as a function of the pilot length,decoding error probability,transmit power and the sub-channel number.Then we reveal significant impact of the above parameters on the effective capacity.A closed-form lower bound of the effective capacity is derived and an alternating optimization based algorithm is proposed to find the optimal pilot length and decoding error probability.Simulation results validate our theoretical analysis and show that the closedform lower bound is very tight.In addition,through the simulations of the optimized effective capacity,insights for pilot length and decoding error probability optimization are provided to evaluate the optimal parameters in realistic systems.

Assessment of the Recent Hydromorphological Features of Nokoue Lake and Its Channels (South-East Benin)

Based on 2022 and 2023 hydrometric data and satellite images (Sentinel 2022, SPOT 2010), this study aims to present the Nokoué Lake and its channels’ re-cent hydromorphological characteristics. Integrating flow, tributary morphology, and topography data determined specific power values along the axes studied. The values obtained range from 2.69 to 12.92 W/m2 for Ouémé River and 2.46 to 10.99 W/m2 for Sô River. The resulting water erosion on banks and bottoms is of linear, areolar, or gully and claw types. Lake bathymetry varies from -0.5 to -2.6 m (low flow period) and -1 to -4 m;in the Ouémé, Sô, and Totchè rivers, it varies from -5 m to -7 m, reaching -10 m at the Cotonou channel entrance (flood period). Bathymetric profiles reveal varied “U”, “V” and “Intermediate” bottom morphologies, influenced by erosion/sedimentation processes and human activities. The flow facies identified are lentic in the northern tributaries and lotic in the Cotonou and Totchè canals. Spatial analysis identified nine (09) thematic classes. In 2022, the surface area of the water body has increased from 274 km2 at low water to 280 km2 at high water, whereas in 2010 (a recent year of exceptional flooding), the surface area was 270 km2 at low water and 277 km2 at high water. Significant changes in land use are observed between 2010 and 2022. The floodplain area decreased slightly, from 421 km2 in 2010 (year of exceptional flooding) to 419 km2 in 2022. The evolution of land use shows a progressive expansion of the urban environment to the detriment of the natural environment. In the medium to long term, this trend could threaten the hydromorphological balance and even the existence of this important lagoon ecosystem.

The variation in basal channels and basal melt rates of Pine Island Ice Shelf

In recent years,there has been a significant acceleration in the thinning,calving and retreat of the Pine Island Ice Shelf(PIIS).The basal channels,results of enhanced basal melting,have the potential to significantly impact the stability of the PIIS.In this study,we used a variety of remote sensing data,including Landsat,REMA DEM,ICESat-1 and ICESat-2 satellite altimetry observations,and Ice Bridge airborne measurements,to study the spatiotemporal changes in the basal channels from 2003 to 2020 and basal melt rate from 2010 to 2017 of the PIIS under the Eulerian framework.We found that the basal channels are highly developed in the PIIS,with a total length exceeding 450 km.Most of the basal channels are ocean-sourced or groundingline-sourced basal channels,caused by the rapid melting under the ice shelf or near the groundingline.A raised seabed prevented warm water intrusion into the eastern branch of the PIIS,resulting in a lower basal melt rate in that area.In contrast,a deepsea trough facilitates warm seawater into the mainstream and the western branch of the PIIS,resulting in a higher basal melt rate in the main-stream,and the surface elevation changes above the basal channels of the mainstream and western branch are more significant.The El Ni?o event in 2015–2016 possibly slowed down the basal melting of the PIIS by modulating wind field,surface sea temperature and depth seawater temperature.Ocean and atmospheric changes were driven by El Ni?o,which can further explain and confirm the changes in the basal melting of the PIIS.

Temperature Drop of Molten Metals in Open Channels

The temperature drop of molten metal flowing in open channels is numerically determined. Rectangular, trapezoidal and triangular geometries are considered. The overall heat transfer coefficients for the bottom, side walls and free surface of the channel have been taken from the literature. For each geometry, the volumetric flow rate, mean residence time and temperature drop as a function of the channel inclination angle were determined. The rectangular and trapezoidal geometries present the smallest temperature drops, while the triangular geometry presents the greatest temperature drop. The factors that most affect this drop are the value of the free surface area of the channel, and the average residence time of the molten metal in the channel.

K^+ Channels and Their Effects on Membrane Potential in Rat Bronchial Smooth Muscle Cells

In order to investigate the K+ channels and their effects on resting membrane potential (Em) and excitability in rat bronchial smooth muscle cells (BSMCs), the components of outward K+ channel currents and the effects of K+ channels on Em and tension in rat bronchial smooth muscle were observed by using standard whole-cell recording of patch clamp and isometric tension recording techniques. The results showed that under resting conditions, total outward K+ channel currents in freshly isolated BSMCs were unaffected by ATP-sensitive K+ channel blocker. There were two types of K+ currents: voltage-dependent delayed rectifier K+ channel (Kv) and large conductance calcium-activated K+ channel (BKc.) currents. 1 mmol/L 4-aminopyridine (4-AP, an inhibitor of Kv) caused a significant depolarization (from -8. 7±5. 9 mV to -25. 4±3. 1 mV, n=18, P<0. 001). In contrast, 1 mmol/L tetraethylammonium (TEA, an inhibitor of BKc.) had no significant effect on Em (from -37. 6±4. 8 mV to -36. 8±4.1mV, n=12, P>0. 05). 4-AP caused a concentration-dependent contraction in resting bronchial strips. TEA had no effect on resting tension, but application of 5 mmol/L TEA resulted in a left shift with bigger pD2(the negative logarithm of the drug concentration causing 50% of maximal effect) (from 6. 27±0. 38 to 6. 89±0. 54, n= 10, P<0. 05) in the concentration-effect curve of endothine-1, and a right shift with smaller pD2(from 8. 10±0. 23 to 7. 69±0. 08, n=10, P<0. 05) in the concentration-effect curve of isoprenaline. It was suggested that in rat BSMCs there may be two types of K+ channels, Kv and BKca, which serve distinct roles. Kv participates in the control of resting Em and tension. BKca is involved in the regulation of relaxation or contraction associated with excitation.