ABSTRACT Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer. Many patients with hepatocellular carcinoma are diagnosed at an advanced stage because the early symptoms are not obvious. For advanced hepatocellular carcinoma, immunotherapy and targeted therapy seem to be a promising direction. Finding a new prognostic marker for hepatocellular carcinoma and exploring its role in

ABSTRACT Most of Solute carrier family-2 (SLC2) members play a key role of facilitative transporters, and glucose transporter (GLUT) proteins encoded by SLC2s can transport hexoses or polyols. However, the function and mechanism of SLC2s remain unclear in human cancers. Here, we explored the dysregulated expression, prognostic values, epigenetic, genetic alterations, and biomolecular network of SLC2s

Abstract Ca2+-activated Cl− channels (CaCCs) perform a multitude of functions including the control of cell excitability, regulation of cell volume and ionic homeostasis, exocrine and endocrine secretion, fertilization, amplification of olfactory sensory function, and control of smooth muscle cell contractility. CaCCs are the translated products of two members (ANO1 and ANO2, also known as TMEM16A

ABSTRACT Cancer is one of the serious diseases that endanger human health and bring a heavy burden to world economic development. Although the current targeted therapy and immunotherapy have achieved initial results, the emergence of drug resistance shows that the existing research is far from enough. In recent years, the tumor microenvironment has been found to be an important condition for tumor

ABSTRACT Estradiol regulates thyroid function, and chloride channels are involved in the regulation of thyroid function. However, little is known about the role of chloride channels in the regulation of thyroid functions by estrogen. In this study, the effects of estrogen on chloride channel activities in human thyroid Nthy-ori3-1 cells were therefore investigated using the whole cell patch-clamp technique

ABSTRACT Nicotinic acetylcholine receptors (nAChRs) are members of the “cys-loop” ligand-gated ion channel superfamily that play important roles in both the peripheral and central system. At the neuromuscular junction, the endplate current is induced by ACh binding and nAChR activation, and then, the current declines to a small steady state, even though ACh is still bound to the receptors. The kinetics

ABSTRACT Metabolic reprogramming is common in various cancers. Targeting metabolism to treat tumors is a hot research topic at present. Among them, changes in glucose metabolism in cancer have been widely studied. The Warburg effect maintains a high metabolic level in the tumor, accompanied by changes in glucose transporters. The transmembrane transport of sugar was previously thought to be mediated

ABSTRACT Endocannabinoids are a group of endogenous mediators derived from membrane lipids, which are implicated in a wide variety of physiological functions such as blood pressure regulation, immunity, pain, memory, reward, perception, reproduction, and sleep. N-Arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG) represent two major endocannabinoids in the human body and they

ABSTRACT Mathematical models for the action potential (AP) generation of the electrically excitable cells including the heart are involved different mechanisms including the voltage-dependent currents with nonlinear time- and voltage-gating properties. From the shape of the AP waveforms to the duration of the refractory periods or heart rhythms are greatly affected by the functions describing the features

ABSTRACT Melanoma is a type of cancer with a relatively poor prognosis. The development of immunotherapy for the treatment of patients with melanoma has drawn considerable attention in recent years. It is of great clinical significance to identify novel promising prognostic biomarkers and to explore their roles in the immune microenvironment. The solute carrier (SLC) superfamily is a group of transporters

ABSTRACT KCNMA1-linked channelopathy is an emerging neurological disorder characterized by heterogeneous and overlapping combinations of movement disorder, seizure, developmental delay, and intellectual disability. KCNMA1 encodes the BK K+ channel, which contributes to both excitatory and inhibitory neuronal and muscle activity. Understanding the basis of the disorder is an important area of active

ABSTRACT Voltage-gated calcium channels (VGCCs) represent key regulators of the calcium influx through the plasma membrane of excitable cells, like neurons. Activated by the depolarization of the membrane, the opening of VGCCs induces very transient and local changes in the intracellular calcium concentration, known as calcium nanodomains, that in turn trigger calcium-dependent signaling cascades and

ABSTRACT The mechanosensitive channel Piezo1 is a crucial membrane mechanosensor ubiquitously expressed in mammalian cell types. Critical to its function in mechanosensory transduction is its ability to change conformation in response to applied mechanical force. Here, we interrogate the role of the anchor domain in the mechanically induced gating of human Piezo1 channels. Using the insertion of glycine

ABSTRACT The mitochondrial BKCa channel (mitoBKCa) is a splice variant of plasma membrane BKCa (Maxi-K, BKCa, Slo1, KCa1.1). While a high-resolution structure of mitoBKCa is not available yet, functional and structural studies of the plasma membrane BKCa have provided important clues on the gating of the channel by voltage and Ca2+, as well as the interaction with auxiliary subunits. To date, we know

ABSTRACT Transient Receptor Potential Melastatin 3 (TRPM3) is a Ca2+ permeable nonselective cation channel, activated by heat and chemical agonists, such as the endogenous neuro-steroid Pregnenolone Sulfate (PregS) and the chemical compound CIM0216. TRPM3 is expressed in peripheral sensory neurons of the dorsal root ganglia (DRG), and its role in noxious heat sensation in mice is well established.

ABSTRACT Our previous studies have implicated CaV3.2 isoform of T-type Ca2+ channels (T-channels) in the development of postsurgical pain. We have also previously established that different T-channel antagonists can alleviate in vivo postsurgical pain. Here we investigated the analgesic potential of another T-channel blocker and endogenous antioxidant molecule, α-lipoic acid (ALA), in a postsurgical

ABSTRACT Vitamin D is known to elicit many biological effects in diverse tissue types and is thought to act almost exclusively upon its canonical receptor within the nucleus, leading to gene transcriptional changes and the subsequent cellular response. However, not all the observed effects of vitamin D can be attributed to this sole mechanism, and other cellular targets likely exist but remain to be

ABSTRACT As the most common histologic subtype of renal cancer, clear cell renal cell carcinoma (ccRCC) poses a serious threat to public health. However, there are no specific molecular-targeted drugs for ccRCC at present. Human ATP-binding cassette (ABC) transporter family plays an important role in homeostasis maintenance. This study aimed to evaluate the potential diagnostic value of ABC genes in

ABSTRACT Articular cartilage consists of an extracellular matrix including many proteins as well as embedded chondrocytes. Articular cartilage formation and function are influenced by mechanical forces. Hind limb unloading or simulated microgravity causes articular cartilage loss, suggesting the importance of the healthy mechanical environment in articular cartilage homeostasis and implying a significant

(2021). A bibliometric analysis and review of recent researches on Piezo (2010-2020) Channels: Vol. 15, No. 1, pp. 310-321.

ABSTRACT To explore the research status, hotspots, and trends in research on nicotinic acetylcholine receptor (nAChR) channel. The Web of Science core collection database from 2000 to 2020 was used as the data source. The visual analysis software VOSviewer1.6.16 and Citespace5.7 R3 were used to visualize the studies of the nAChR channel. The national/institutional distribution, journal distribution

ABSTRACT Hydra Na+ channels (HyNaCs) are peptide-gated ion channels of the DEG/ENaC gene family that are directly activated by neuropeptides of the Hydra nervous system. They have previously been successfully characterized in Xenopus oocytes. To establish their expression in mammalian cells, we transiently expressed heteromeric HyNaC2/3/5 in human HEK 293 and monkey COS-7 cells. We found that the expression

ABSTRACT The activity-dependent trafficking of AMPA receptors (AMPAR) mediates synaptic strength and plasticity, while the perturbed trafficking of the receptors of different subunit compositions has been linked to memory impairment and to causing neuropathology. In the spinal cord, nociceptive-induced changes in AMPAR trafficking determine the central sensitization of the dorsal horn (DH): changes

ABSTRACT Background : Mutations in SCN5A that decrease Na current underlie arrhythmia syndromes such as the Brugada syndrome (BrS). SCN5A in humans has two splice variants, one lacking a glutamine at position 1077 (Q1077del) and one containing Q1077. We investigated the effect of splice variant background on loss-of-function and rescue for R1512W, a mutation reported to cause BrS. Methods and results

ABSTRACT The slowly activating delayed rectifier K+ current (I Ks) plays a key role in the repolarization of ventricular action potential in the human heart and is formed by the pore-forming α-subunit encoded by KCNQ1 (Kv7.1) and β-subunit encoded by KCNE1. Evidence suggested that I Ks was regulated through protein kinase C (PKC) pathway, but the mechanism is controversial. This study was designed

ABSTRACT Background : Mutations in SCN5A that decrease Na current underlie arrhythmia syndromes such as the Brugada syndrome (BrS). SCN5A in humans has two splice variants, one lacking a glutamine at position 1077 (Q1077del) and one containing Q1077. We investigated the effect of splice variant background on loss-of-function and rescue for R1512W, a mutation reported to cause BrS. Methods and results

ABSTRACT The slowly activating delayed rectifier K+ current (I Ks) plays a key role in the repolarization of ventricular action potential in the human heart and is formed by the pore-forming α-subunit encoded by KCNQ1 (Kv7.1) and β-subunit encoded by KCNE1. Evidence suggested that I Ks was regulated through protein kinase C (PKC) pathway, but the mechanism is controversial. This study was designed

ABSTRACT N-methyl-D-aspartate receptors (NMDARs) are excitatory ionotropic glutamate receptors expressed throughout the CNS, including in the spinal dorsal horn. The GluN2 subtypes of NMDAR subunit, which include GluN2A, GluN2B, and GluN2D in the dorsal horn, confer NMDARs with structural and functional variability, enabling heterogeneity in synaptic transmission and plasticity. Despite essential roles

ABSTRACT Mutations in the voltage-gated sodium channel Nav1.7 are linked to human pain. The Nav1.7/N1245S variant was described before in several patients suffering from primary erythromelalgia and/or olfactory hypersensitivity. We have identified this variant in a pain patient and a patient suffering from severe and life-threatening orthostatic hypotension. In addition, we report a female patient

ABSTRACT Coronary Artery Disease (CAD) typically kills more people globally each year than any other single cause of death. A better understanding of genetic predisposition to CAD and the underlying mechanisms will help to identify those most at risk and contribute to improved therapeutic approaches. KCNE2 is a functionally versatile, ubiquitously expressed potassium channel β subunit associated with

ABSTRACT Human-induced pluripotent stem cell (hiPSC) and stem cell (hSC) derived cardiomyocytes (CM) are gaining popularity as in vitro model for cardiology and pharmacology studies. A remaining flaw of these cells, as shown by single-cell electrophysiological characterization, is a more depolarized resting membrane potential (RMP) compared to native CM. Most reports attribute this to a lower expression

ABSTRACT Ischemic stroke has a high lethality rate worldwide, and novel treatments are limited. Calcium overload is considered to be one of the mechanisms of cerebral ischemia. Transient receptor potential melastatin 2 (TRPM2) is a reactive oxygen species (ROS)-sensitive calcium channel. Cerebral ischemia-induced TRPM2 activation triggers abnormal intracellular Ca2+ accumulation and cell death, which

ABSTRACT Nociceptor sensitization following nerve injury or inflammation leads to chronic pain. An increase in the nociceptor hyperpolarization-activated current, Ih, is observed in many models of pathological pain. Pharmacological blockade of Ih prevents the mechanical and thermal hypersensitivity that occurs during pathological pain. Alterations in the Hyperpolarization-activated Cyclic Nucleotide-gated

ABSTRACT A fundamental mechanism that drives the propagation of electrical signals in the nervous system is the activation of voltage-gated sodium channels. The sodium channel subtype Nav1.7 is critical for the transmission of pain-related signaling, with gain-of-function mutations in Nav1.7 resulting in various painful pathologies. Loss-of-function mutations cause complete insensitivity to pain and

ABSTRACT Structural studies with an α subunit fragment of voltage-gated calcium (CaV) channels in complex with the CaVβ subunits revealed a high homology between the various CaVα-β subunits, predicting that targeting of this interface would result in nonselective compounds. Despite this likelihood, my laboratory initiated a rational structure-based screening campaign focusing on “hot spots” on the

ABSTRACT Ion channels underlie all forms for electrical signaling including the transmission of information about harmful events. Voltage-gated calcium ion channels have dual function, they support electrical signaling as well as intracellular calcium signaling through excitation-dependent calcium entry across the plasma membrane. Mechanisms that regulate ion channel forms and actions are essential

ABSTRACT Acid-sensing ion channel 3 (ASIC3) belongs to the epithelial sodium channel/degenerin (ENaC/DEG) superfamily. There are 7 different ASIC subunits encoded by 5 different genes. Most ASIC subunits form trimeric ion channels that upon activation by extracellular protons mediate a transient inward current inducing cellular excitability. ASIC subunits exhibit differential tissue expression and

ABSTRACT -->Low voltage-activated Cav1.3 L-type Ca2+-channels are key regulators of neuronal excitability controlling neuronal development and different types of learning and memory. Their physiological functions are enabled by their negative activation voltage-range, which allows Cav1.3 to be active at subthreshold voltages. Alternative splicing in the C-terminus of their pore-forming α1-subunits

ABSTRACT The voltage-gated sodium channel Nav1.8 mediates the tetrodotoxin-resistant (TTX-R) Na+ current in nociceptive primary sensory neurons, which has an important role in the transmission of painful stimuli. Here, we describe the functional modulation of the human Nav1.8 α-subunit in Xenopus oocytes by auxiliary β subunits. We found that the β3 subunit down-regulated the maximal Na+ current amplitude

ABSTRACT Ion channels play pivotal role in the physiological and pathological function of immune cells. As immune cells represent a functionally diverse population, subtype-specific functional studies, such as single-cell electrophysiology require proper subset identification and separation. Magnetic-activated cell sorting (MACS) techniques provide an alternative to fluorescence-activated cell sorting

ABSTRACT In the last 5 years inhibitors of the potassium channel KV1.3 have been shown to reduce neuroinflammation in rodent models of ischemic stroke, Alzheimer’s disease, Parkinson’s disease and traumatic brain injury. At the systemic level these beneficial actions are mediated by a reduction in microglia activation and a suppression of pro-inflammatory cytokine and nitric oxide production. However

ABSTRACT In this brief report, we demonstrate that the Cav3.3 T-type voltage-gated calcium channel subtype is involved in our FRICT-ION model of chronic trigeminal neuropathic pain. We first showed that the Cacna1i gene encoding Cav3.3 is significantly upregulated in whole trigeminal ganglia of FRICT-ION mice compared to controls at week 10 post-injury. We confirmed protein upregulation of Cav3.3 compared

ABSTRACT The cardiac late sodium current (INa,late) is the small sustained component of the sodium current active during the plateau phase of the action potential. Several studies demonstrated that augmentation of the current can lead to cardiac arrhythmias; therefore, INa,late is considered as a promising antiarrhythmic target. Fundamentally, enlarged INa,late increases Na+ influx into the cell, which

ABSTRACT To explore the clinical and genetic characteristics of five families with primary periodic paralysis (PPP). We reviewed clinical manifestations, laboratory results, electrocardiogram, electromyography, muscle biopsy, and genetic analysis from five families with PPP. Five families with PPP included: hypokalemic periodic paralysis type 1 (HypoPP1, CACNA1S, 1/5), hypokalemic periodic paralysis

Abstract In this brief report, we demonstrate that the Cav3.3 T-type voltage-gated calcium channel subtype is involved in our FRICT-ION model of chronic trigeminal neuropathic pain. We first showed that the Cacna1i gene encoding Cav3.3 is significantly upregulated in whole trigeminal ganglia of FRICT-ION mice compared to controls at week 10 post-injury. We confirmed protein upregulation of Cav3.3 compared

ABSTRACT Transient receptor potential melastatin 8 (TRPM8) channels play a central role in the detection of environmental cold temperatures in the somatosensory system. TRPM8 is found in a subset of unmyelinated (C-type) afferents located in the dorsal root (DRG) and trigeminal ganglion (TG). Cold hypersensitivity is a common symptom of neuropathic pain conditions caused by cancer therapy, spinal cord

(2020). Bibliometric analysis of chloride channel research (2004–2019) Channels: Vol. 14, No. 1, pp. 393-402.

ABSTRACT The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted an urgent need to identify effective medicines for the prevention and treatment of the disease. A comparative analysis between SARS-CoV-2 and Hepatitis C Virus (HCV) can expand the available knowledge regarding the virology and potential drug targets against these viruses. Interestingly

ABSTRACT Voltage-gated calcium channels (VGCCs) are critical for Ca2+ influx into all types of excitable cells, but their exact function is still poorly understood. Recent reconstruction of homology models for all human VGCCs at atomic resolution provides the opportunity for a structure-based discussion of VGCC function and novel insights into the mechanisms underlying Ca2+ selective flux through these

ABSTRACT Voltage-gated Ca2+ channels are typically integrated in a complex network of protein-protein-interactions, also referred to as Ca2+ channel nanodomains. Amongst the neuronal CaV2 channel family, CaV2.2 is of particular importance due to its general role for signal transmission from the periphery to the central nervous system, but also due to its significance for pain perception. Thus, CaV2

ABSTRACT Cytosolic Ca2+ concentration ([Ca2+ ]) has an important role in spermatozoa and hence it regulates fertilization. In male germinal cells, there are indirect evidences that this ion could regulate physiological processes in spermatogenesis. Since little is known about Ca 2+ homeostasis in spermatogenic cells, in this work we propose a mathematical model that accounts for experimental [Ca2+

ABSTRACT Arabidopsis thaliana contains five tandem-pore domain potassium channels, TPK1-TPK5 and the related one-pore domain potassium channel, KCO3. Although KCO3 is unlikely to be an active channel, it still has a physiological role in plant cells. TPK2 is most similar to KCO3 and both are localized to the tonoplast. However, their function remains poorly understood. Here, taking advantage of the

ABSTRACT Mechanosensitive (MS) ion channels are widespread mechanisms for cellular mechanosensation that can be directly activated by increasing membrane tension. The well-studied MscS family of MS ion channels is found in bacteria, archaea, and plants. MscS-Like (MSL)1 is localized to the inner mitochondrial membrane of Arabidopsis thaliana, where it is required for normal mitochondrial responses

ABSTRACT Ca2+-induced Ca2+ release (CICR) from sarcoplasmic reticulum is a finely tuned process responsible for cardiac excitation and contraction. The ubiquitin–proteasome system (UPS) as a major degradative system plays a crucial role in the maintenance of Ca2+ homeostasis. The E3 component N-recognin (UBR) subfamily is a part of the UPS; however, the role of UBR in regulating cardiac CICR is unknown

The KCNH family comprises the ERG, EAG, and ELK voltage-activated, potassium-selective channels. Distinct from other K channels, KCNH channels contain unique structural domains, including a PAS (Per-Arnt-Sim) domain in the N-terminal region and a CNBHD (cyclic nucleotide-binding homology domain) in the C-terminal region. The intracellular PAS domains and CNBHDs interact directly and regulate some of

ABSTRACT The cardiac voltage-gated sodium channel Nav1.5 conducts the rapid inward sodium current crucial for cardiomyocyte excitability. Loss-of-function mutations in its gene SCN5A are linked to cardiac arrhythmias such as Brugada Syndrome (BrS). Several BrS-associated mutations in the Nav1.5 N-terminal domain (NTD) exert a dominant-negative effect (DNE) on wild-type channel function, for which mechanisms

ABSTRACT CACNA1 C, which codes for the Cav1.2 isoform of L-type Ca2+ channels (LTCCs), is a prominent risk gene in neuropsychiatric and neurodegenerative conditions. A role forLTCCs, and Cav1.2 in particular, in transcription-dependent late long-term potentiation (LTP) has long been known. Here, we report that elimination of Cav1.2 channels in glutamatergic neurons also impairs theta burst stimulation

ABSTRACT TRPC3 is a Ca2+-permeable cation channel commonly activated by the G-protein coupled receptors (GPCR) and mechanical distortion of the plasma membrane. TRPC3-mediated Ca2+ influx has been implicated in a variety of signaling processes in both excitable and non-excitable cells. Kidneys play a commanding role in maintaining whole-body homeostasis and setting blood pressure. TRPC3 is expressed

ABSTRACT The elevated intracellular Ca2+ and oxidative stress are well-reported mechanisms behind renal tubular epithelial injury initiated by various insults. Given that TRPV4 and connexin43 (Cx43) channels are activated by a wide range of stimuli and regulate both intracellular Ca2+ and redox status, we speculated an involvement of these channels in renal tubular cell injury. Here, we tested this

ABSTRACT Low voltage activated (ICa-LVA) calcium currents including Cav1.3 and T-type calcium current (ICa-T) have not been reported in adult human left ventricular myocytes (HLVMs). We tried to examine their existence and possible correlation with etiology and patient characteristics in a big number of human LVMs isolated from explanted terminally failing (F) hearts, failing hearts with left ventricular