• anoctamin 1
• calcium activated chloride channel
• chloride cell
• euryhaline fish
• osmoregulation

• Animals
• Oryzias/physiology
• Oryzias/metabolism
• Oryzias/genetics
• Fresh Water
• Seawater
• Gills/metabolism
• Cystic Fibrosis Transmembrane Conductance Regulator/genetics
• Cystic Fibrosis Transmembrane Conductance Regulator/metabolism
• Acclimatization/physiology
• Anoctamin-1/metabolism
• Anoctamin-1/genetics
• Hydrocortisone/pharmacology
• Gene Expression Regulation/physiology
• Gene Expression Regulation/drug effects
• RNA, Messenger/metabolism
• RNA, Messenger/genetics

• This work was supported by the Sasakawa Scientific Research Grant from The Japan Science Society and by JSPS KAKENHI (Grant Number 23K23922).

• Alantolactone
• CFTR
• CaCCs
• Isoalantolactone
• Secretory diarrhea
• Sesquiterpene lactone

• Rats
• Mice
• Animals
• Cystic Fibrosis Transmembrane Conductance Regulator
• Diarrhea/drug therapy
• Diarrhea/metabolism
• Chloride Channels/metabolism
• Intestinal Mucosa/metabolism
• Rotavirus
• Rats, Inbred F344
• Lactones/pharmacology
• Lactones/therapeutic use
• Sesquiterpenes/pharmacology
• Sesquiterpenes/therapeutic use
• Sesquiterpenes/metabolism
• Chlorides/metabolism

• VEGF-A
• bestrophin1
• head and neck squamous cell carcinoma
• monocytes
• tumor microenvironment

• 2021-I2M-1-050 (J.M.) CAMS Innovation Fund for Medical Sciences
• BJ-2022-118 (J.M.) National High Level Hospital Clinical Research Funding
• 82003264 (Q.T.) National Natural Science Foundation of China
• 82203534 (L.Z.) National Natural Science Foundation of China

• Gastric cancer
• HIF
• Hypoxia
• Ion channel
• ROS
• Tumor microenvironment

• Disease Progression
• Gene Expression Regulation, Neoplastic
• Humans
• Hypoxia/genetics
• Hypoxia/metabolism
• Hypoxia/pathology
• Hypoxia-Inducible Factor 1, alpha Subunit/genetics
• Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
• Ion Channels/genetics
• Ion Channels/metabolism
• Membrane Transport Proteins/genetics
• Membrane Transport Proteins/metabolism
• Reactive Oxygen Species/metabolism
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology
• Tumor Microenvironment/genetics

• 81860103 the National Natural Science Foundation of China
• 82070536 the National Natural Science Foundation of China
• 81660098 the National Natural Science Foundation of China
• 2017-5608 the Outstanding Scientific Youth Fund of Guizhou Province
• the National Natural Science Foundation of China
• the 15851 Talent Projects of Zunyi City

P2X7 receptors (P2X7) are cationic channels involved in many diseases. Following their activation by extracellular ATP, distinct signaling pathways are triggered, which lead to various physiological responses such as the secretion of pro-inflammatory cytokines or the modulation of cell death. P2X7 also exhibit unique behaviors, such as “macropore” formation, which corresponds to enhanced large molecule cell membrane permeability and current facilitation, which is caused by prolonged activation. These two phenomena have often been confounded but, thus far, no clear mechanisms have been resolved. Here, by combining different approaches including whole-cell and single-channel recordings, pharmacological and biochemical assays, CRISPR/Cas9 technology and cell imaging, we provide evidence that current facilitation and macropore formation involve functional complexes comprised of P2X7 and TMEM16, a family of Ca²⁺-activated ion channel/scramblases. We found that current facilitation results in an increase of functional complex-embedded P2X7 open probability, a result that is recapitulated by plasma membrane cholesterol depletion. We further show that macropore formation entails two distinct large molecule permeation components, one of which requires functional complexes featuring TMEM16F subtype, the other likely being direct permeation through the P2X7 pore itself. Such functional complexes can be considered to represent a regulatory hub that may orchestrate distinct P2X7 functionalities.

• ATP sensitization
• P2X7
• anoctamin
• cell permeabilization
• ion channel
• purinergic receptor

• Abdominal surgery
• Complication
• Inflammation
• Peritoneal adhesions
• Physiopathology
• Therapeutics

• HO-1
• Norcepharadione B
• PI3K/Akt
• VSOR Cl−channel
• cell volume
• oxidative stress

• cell micro-environment
• cell volume
• mechanobiology
• mechanotransduction

• Giardia Intestinalis
• Xenopus laevis
• Chloride channels
• electrophysiology

• Animals
• Calcium/metabolism
• Chloride Channels/biosynthesis
• Chloride Channels/genetics
• Chloride Channels/metabolism
• Electrophysiological Phenomena
• Female
• Giardia lamblia/genetics
• Giardia lamblia/growth & development
• Hydrogen-Ion Concentration
• Injections
• Membrane Potentials
• Oocytes/cytology
• Oocytes/metabolism
• RNA, Messenger/administration & dosage
• RNA, Messenger/genetics
• RNA, Protozoan/administration & dosage
• RNA, Protozoan/genetics
• Trophozoites/genetics
• Trophozoites/growth & development
• Xenopus laevis/genetics
• Xenopus laevis/metabolism

• Ttyh
• Tweety-homolog
• VRAC
• Volume regulation
• Volume-regulated anion channel

Volume-regulated anion channels (VRACs) are key players in regulatory volume decrease of vertebrate cells by mediating the extrusion of chloride and organic osmolytes. They play additional roles in various physiological processes beyond their role in osmotic volume regulation. VRACs are formed by heteromers of LRRC8 proteins; LRRC8A (also called SWELL1) is an essential subunit that combines with any of its paralogs, LRRC8B–E, to form hexameric VRAC complexes. The subunit composition of VRACs determines electrophysiological characteristics of their anion transport such as single-channel conductance, outward rectification, and depolarization-dependent inactivation kinetics. In addition, differently composed VRACs conduct diverse substrates, such as LRRC8D enhancing VRAC permeability to organic substances like taurine or cisplatin. Here, after a recapitulation of the biophysical properties of VRAC-mediated ion and osmolyte transport, we summarize the insights gathered since the molecular identification of VRACs. We describe the recently solved structures of LRRC8 complexes and discuss them in terms of their structure-function relationships. These studies open up many potential avenues for future research.

• Fisetin
• Flavonoids
• Flavoxate
• Galangin
• Luteolin
• Quercetin
• VRAC

• Anions/metabolism
• Cell Proliferation
• Cell Size
• Flavonoids/chemistry
• Flavonoids/pharmacology
• HEK293 Cells
• Human Umbilical Vein Endothelial Cells/drug effects
• Human Umbilical Vein Endothelial Cells/physiology
• Humans
• Ion Channels/antagonists & inhibitors
• Membrane Potentials
• Membrane Transport Modulators/chemistry
• Membrane Transport Modulators/pharmacology

The effect of toxic concentrations of La³⁺ on the Ca, K, Na, Mg, and Cl channels of planaria was investigated through the use of various agonists and antagonists to those channels. It was demonstrated that La exerts its toxic effects through L-type, but not T-type, Ca channels. La also demonstrated activity at Na, K, Mg, and Cl channels, but, these effects were most likely mediated by other effects of La on Ca activity. However, these interactions appear to be very complex and confounded by oxidative stresses. The study also introduces a planaria stress scale which allows the effects of toxic substances to be examined on a continuum.

• calcium
• chloride
• ion channels
• lanthanum
• magnesium
• planaria
• potassium
• sodium
• toxicology

• Actins/chemistry
• Cell Line, Tumor
• Cell Size
• Chlorides/metabolism
• Electrophysiological Phenomena
• Extracellular Space/metabolism
• Humans
• Intracellular Space/metabolism
• Potassium/metabolism
• Protein Multimerization
• Protein Structure, Quaternary
• Sodium/metabolism

• R21 CA152779 NCI NIH HHS
• U54 CA210173 NCI NIH HHS
• R01 GM114675 NIGMS NIH HHS
• R25 GM056929 NIGMS NIH HHS
• R01 DC000354 NIDCD NIH HHS

• NADPH oxidase
• chloride
• hypochlorous acic
• monocytes/macrophages
• neutrophils
• oxidants

Gastric cancer (GC) is a common disease with few effective treatment choices and poor prognosis, and has the second-highest mortality rates among all cancers worldwide. Dysregulation and/or malfunction of ion channels or aquaporins (AQPs) are common in various human cancers. Furthermore, ion channels are involved in numerous important aspects of the tumor aggressive phonotype, such as proliferation, cell cycle, apoptosis, motility, migration, and invasion. Indeed, by localizing in the plasma membrane, ion channels or AQPs can sense and respond to extracellular environment changes; thus, they play a crucial role in cell signaling and cancer progression. These findings have expanded a new area of pharmaceutical exploration for various types of cancer, including GC. The involvement of multiple ion channels, such as voltage-gated potassium and sodium channels, intracellular chloride channels, ‘transient receptor potential’ channels, and AQPs, which have been shown to facilitate the pathogenesis of other tumors, also plays a role in GC. In this review, an overview of ion channel and aquaporin expression and function in carcinogenesis of GC is presented. Studies of ion channels or AQPs will advance our understanding of the molecular genesis of GC and may identify novel and effective targets for the clinical application of GC.

• Aquaporin
• Calcium
• Chloride
• Gastric cancer
• Ion channels
• Potassium
• Sodium
• Therapeutic target

Chloride is the most abundant permeable anion in the cell, and numerous studies in the last two decades highlight the great importance and broad physiological role of chloride currents mediated anion transport. They participate in a multiplicity of key processes, as for instance, the regulation of electrical excitability, apoptosis, cell cycle, epithelial secretion and neuronal excitability. In addition, dysfunction of Cl⁻ channels is involved in a variety of human diseases such as epilepsy, osteoporosis and different cancer types. Historically, chloride channels have been of less interest than the cation channels. In fact, there seems to be practically no quantitative studies of the dynamics of chloride currents. Here, for the first time, we have quantitatively studied experimental calcium-activated chloride fluxes belonging to Xenopus laevis oocytes, and the main results show that the experimental Cl⁻ currents present an informational structure characterized by highly organized data sequences, long-term memory properties and inherent “crossover” dynamics in which persistent correlations arise at short time intervals, while anti-persistent behaviors become dominant in long time intervals. Our work sheds some light on the understanding of the informational properties of ion currents, a key element to elucidate the physiological functional coupling with the integrative dynamics of metabolic processes.

• ACLT
• Anion channel
• Apoptosis
• Cartilage
• Caspase
• Chloride channel
• Ion channels
• Osteoarthritis

• Animals
• Humans
• Ion Channels/metabolism
• Membrane Proteins/metabolism
• Membrane Transport Proteins/metabolism

• Chloride Channel-3
• P-glycoprotein
• Peritoneal Adhesions

• ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics
• ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism
• Animals
• Cells, Cultured
• Chloride Channels/metabolism
• Fibroblasts/metabolism
• Gene Silencing
• Humans
• Laparotomy/adverse effects
• Peritoneal Diseases/etiology
• Peritoneal Diseases/metabolism
• Phosphorylation
• Postoperative Complications/metabolism
• Protein Processing, Post-Translational
• Rats
• Up-Regulation

• LRRC8A
• TMEM16A
• VRAC
• VSOAC
• anoctamins
• apoptotic volume decrease
• regulatory volume decrease

Mechanical transduction by ion channels occurs in all cells. The physiological functions of these channels have just begun to be elaborated, but if we focus on the upper animal kingdom, these channels serve the common sensory services such as hearing and touch, provide the central nervous system with information on the force and position of muscles and joints, and they provide the autonomic system with information about the filling of hollow organs such as blood vessels. However, all cells of the body have mechanosensitive channels (MSCs), including red cells. Most of these channels are cation selective and are activated by bilayer tension. There are also K⁺ selective MSCs found commonly in neurons where they may be responsible for both general anesthesia and knockout punches in the boxing ring by hyperpolarizing neurons to reduce excitability. The cationic MSCs are typically inactive under normal mechanical stress, but open under pathologic stress. The channels are normally inactive because they are shielded from stress by the cytoskeleton. The cationic MSCs are specifically blocked by the externally applied peptide GsMtx4 (aka, AT-300). This is the first drug of its class and provides a new approach to many pathologies since it is nontoxic, non-immunogenic, stable in a biological environment and has a long pharmacokinetic lifetime. Pathologies involving excessive stress are common. They produce cardiac arrhythmias, contraction in stretched dystrophic muscle, xerocytotic and sickled red cells, etc. The channels seem to function primarily as “fire alarms”, providing feedback to the cytoskeleton that a region of the bilayer is under excessive tension and needs reinforcing. The eukaryotic forms of MSCs have only been cloned in recent years and few people have experience working with them. “Newbies” need to become aware of the technology, potential artifacts, and the fundamentals of mechanics. The most difficult problem in studying MSCs is that the actual stimulus, the force applied to the channel, is not known. We don’t have direct access to the channels themselves but only to larger regions of the membrane as seen in patches. Cortical forces are shared by the bilayer, the cytoskeleton and the extracellular matrix. How much of an applied stimulus reaches the channel is unknown. Furthermore, many of these channels exist in spatial domains where the forces within a domain are different from forces outside the domain, although we often hope they are proportional. This review is intended to be a guide for new investigators who want to study mechanosensitive ion channels.

• Channel
• Mechanical
• Patch
• Force
• Tension
• Bilayer
• Domain
• Osmotic
• Transduction
• Biomechanics

Low-intensity lasers are used for prevention and management of oral mucositis induced by anticancer therapy, but the effectiveness of treatment depends on the genetic characteristics of affected cells. This study evaluated the survival and induction of filamentation of Escherichia coli cells deficient in the nucleotide excision repair pathway, and the action of T₄endonuclease V on plasmid DNA exposed to low-intensity red and near-infrared laser light. Cultures of wild-type (strain AB1157) E. coli and strain AB1886 (deficient in uvrA protein) were exposed to red (660 nm) and infrared (808 nm) lasers at various fluences, powers and emission modes to study bacterial survival and filamentation. Also, plasmid DNA was exposed to laser light to study DNA lesions produced in vitro by T₄endonuclease V. Low-intensity lasers:i) had no effect on survival of wild-type E. coli but decreased the survival of uvrA protein-deficient cells,ii) induced bacterial filamentation, iii) did not alter the electrophoretic profile of plasmids in agarose gels, andiv) did not alter the electrophoretic profile of plasmids incubated with T₄ endonuclease V. These results increase our understanding of the effects of laser light on cells with various genetic characteristics, such as xeroderma pigmentosum cells deficient in nucleotide excision pathway activity in patients with mucositis treated by low-intensity lasers.

• apoptosis
• cell volume regulation
• hypoxia
• lung function
• membrane dynamics
• mitochondrial function

Pancreatic ductal adenocarcinoma (PDAC) has one of the worst survival rates of all cancers. ANO1 (TMEM16A) is a recently identified Ca²⁺-activated Cl⁻ channel (CaCC) that is upregulated in several tumors. Although ANO1 was subject to extensive studies in the recent years, its pathophysiological function has only been poorly understood. The aim of the present study is to establish the significance of ANO1 in PDAC behavior and demarcate its roles in PDAC from those of the volume-regulated anion channel (VRAC). We performed qPCR and Western blot measurements on different PDAC cell lines (Panc-1, Mia PaCa 2, Capan-1, AsPC-1, BxPC-3) and compared the results to those obtained in a human pancreatic ductal epithelium (HPDE) cell line. All cancer cell lines showed an upregulation of ANO1 on mRNA and protein levels. Whole-cell patch-clamp recordings identified large Ca²⁺ and voltage-dependent Cl⁻ currents in PDAC cells. Using siRNA knockdown of ANO1 and three ANO1 inhibitors (T16A_inh-A01, CaCC_inh-A01, and NS3728), we found that ANO1 is the main constituent of CaCC current in PDAC cells. We further characterized these three inhibitors and found that they had unspecific effects on the free intracellular calcium concentration. Functional studies on PDAC behavior showed that surprisingly inhibition of ANO1 did not influence cellular proliferation. On the other hand, we found ANO1 channel to be pivotal in PDAC cell migration as assessed in wound healing experiments.