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.

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.

Isolation of Protoplast and Ion Channel Recording in Plasma Membrane of Suspension Cells of Populus euphratica

The authors used suspension cells of Populus euphratica to isolate protoplast in the present study. Protoplasts were successfully obtained after 4 hours incubation in enzyme solution containing 1 0% cellulase “onozuka” R\|10, 0\^01% pectolyase Y\|23,0\^15% macerozyme R\|10 and 0\^1% hemicellulase at 25℃. Outward and inward single channels in plasma membrane were observed using cell\|attached recording of patch\|clamp technique. In this study, single channel records showed that more than one species of channel were obtained. These attempts in protoplast isolation and ion channel recording offers the opportunity to characterize cellular mechanisms of salt tolerance in tree species.

Molecular Mechanisms of Cyclic Nucleotide-Gated Ion Channel Gating

Cyclic nucleotide-gated ion channels （CNGs） are distributed most widely in the neuronal cell. Great progress has been made in molecular mechanisms of CNG channel gating in the recent years. Results of many experiments have indicated that the stoichiometry and assembly of CNG channels affect their property and gating. Experiments of CNG mutants and analyses of cys- teine accessibilities show that cyclic nucleotide-binding domains （CNBD） bind cyclic nucleotides and subsequently conformational changes occurred followed by the concerted or cooperative conformational change of all four subunits during CNG gating. In order to provide theoretical assistances for further investigation on CNG channels, especially regarding the disease pathogenesis of ion channels, this paper reviews the latest progress on mechanisms of CNG channels, functions of subunits, processes of subunit assembly, and conformational changes of subunit regions during gating.

基于Ion-Channel的故障多态安全关键系统可靠性研究

通过分析安全关键系统的特点,综合考虑了不同的部件失效模式、维修模式导致系统的不同安全性,建立了部件故障三态、系统故障多态模型.由于系统中每一个部件有工作、安全和危险3种状态,系统状态数随着部件数的增加急剧增加,此情况与生物学中离子通道模型极为相似,作者利用生物学中Ion-Channel理论来聚合系统状态,从而得出一些重要的系统分布和可靠性指标,该模型对系统故障进行了更为细致的划分,提高了分析的准确性.

An optimized recording method to characterize biophysical and pharmacological properties of acid-sensing ion channel

Objective To re-confirm and characterize the biophysical and pharmacological properties of endogenously expressed human acid-sensing ion channel 1a （hASIC1a） current in HEK293 cells with a modified perfusion methods. Methods With cell floating method, which is separating the cultured cell from coverslip and putting the cell in front of perfusion tubing, whole cell patch clamp technique was used to record hASICla currents evoked by low pH external solution. Results Using cell floating method, the amplitude of hASICla currents activated by pH 5.0 in HEK293 cells is twice as large as that by the conventional method where the cells remain attached to coverslip. The time to reach peak at two different recording conditions is （21±5） ms and （270±25） ms, respectively. Inactivation time constants are （496±23） ms and （2284±120） ms, respectively. The cell floating method significantly increases the amiloride potency of block on hASIC 1 a [IC50 is （3.4± 1.1 ） μmol/L and （2.4± 0.9） μmol/L, respectively]. Both recording methods have similar pH activation ECs0 （6.6±0.6, 6.6±0.7, respectively）. Conclusion ASICs channel activation requires fast exchange of extracellular solution with the different pH values. With cell floating method, the presence of hASIC la current was re-confirmed and the biophysical and pharmacological properties of hASIC la channel in HEK293 cells was precisely characterized. This method could be used to study all ASICs and other ligand-gated channels that require fast extracellular solution exchange.

Ion channels, phosphorylation and mammalian sperm apacitation

Sexually reproducing animals require an orchestrated communication between spermatozoa and the egg to generate a new individual. Capacitation, a maturational complex phenomenon that occurs in the female reproductive tract, renders spermatozoa capable of binding and fusing with the oocyte, and it is a requirement for mammalian fertilization. Capacitation encompasses plasma membrane reorganization, ion permeability regulation, cholesterol loss and changes in the phosphorylation state of many proteins. Novel tools to study sperm ion channels, image intracellular ionic changes and proteins with better spatial and temporal resolution, are unraveling how modifications in sperm ion transport and phosphorylation states lead to capacitation. Recent evidence indicates that two parallel pathways regulate phosphorylation events leading to capacitation, one of them requiring activation of protein kinase A and the second one involving inactivation of ser/thr phosphatases. This review examines the involvement of ion transporters and phosphorylation signaling processes needed for spermatozoa to achieve capacitation. Understanding the molecular mechanisms leading to fertilization is central for societies to deal with rising male infertility rates, to develop safe male gamete-based contraceptives and to preserve biodiversity through better assisted fertilization strategies.

Role of ion channels in gastrointestinal cancer

In their seminal papers Hanahan and Weinberg described oncogenic processes a normal cell undergoes to be transformed into a cancer cell.The functions of ion channels in the gastrointestinal(GI)tract influence a variety of cellular processes,many of which overlap with these hallmarks of cancer.In this review we focus on the roles of the calcium(Ca^2+),sodium(Na^+),potassium(K^+),chloride(Cl^-)and zinc(Zn^2+)transporters in GI cancer,with a special emphasis on the roles of the KCNQ1 K+channel and CFTR Cl-channel in colorectal cancer(CRC).Ca^2+is a ubiquitous second messenger,serving as a signaling molecule for a variety of cellular processes such as control of the cell cycle,apoptosis,and migration.Various members of the TRP superfamily,including TRPM8,TRPM7,TRPM6 and TRPM2,have been implicated in GI cancers,especially through overexpression in pancreatic adenocarcinomas and down-regulation in colon cancer.Voltage-gated sodium channels(VGSCs)are classically associated with the initiation and conduction of action potentials in electrically excitable cells such as neurons and muscle cells.The VGSC NaV1.5 is abundantly expressed in human colorectal CRC cell lines as well as being highly expressed in primary CRC samples.Studies have demonstrated that conductance through NaV1.5 contributes significantly to CRC cell invasiveness and cancer progression.Zn2+transporters of the ZIP/SLC39A and ZnT/SLC30A families are dysregulated in all major GI organ cancers,in particular,ZIP4 up-regulation in pancreatic cancer(PC).More than 70 K+channel genes,clustered in four families,are found expressed in the GI tract,where they regulate a range of cellular processes,including gastrin secretion in the stomach and anion secretion and fluid balance in the intestinal tract.Several distinct types of K+channels are found dysregulated in the GI tract.Notable are hERG1 upregulation in PC,gastric cancer(GC)and CRC,leading to enhanced cancer angiogenesis and invasion,and KCNQ1 down-regulation in CRC,where KCNQ1 expression is associated with enhanced disease-free survival in stage II,III,and IV disease.Cl-channels are critical for a range of cellular and tissue processes in the GI tract,especially fluid balance in the colon.Most notable is CFTR,whose deficiency leads to mucus blockage,microbial dysbiosis and inflammation in the intestinal tract.CFTR is a tumor suppressor in several GI cancers.Cystic fibrosis patients are at a significant risk for CRC and low levels of CFTR expression are associated with poor overall disease-free survival in sporadic CRC.Two other classes of chloride channels that are dysregulated in GI cancers are the chloride intracellular channels(CLIC1,3&4)and the chloride channel accessory proteins(CLCA1,2,4).CLIC1&4 are upregulated in PC,GC,gallbladder cancer,and CRC,while the CLCA proteins have been reported to be down-regulated in CRC.In summary,it is clear,from the diverse influences of ion channels,that their aberrant expression and/or activity can contribute to malignant transformation and tumor progression.Further,because ion channels are often localized to the plasma membrane and subject to multiple layers of regulation,they represent promising clinical targets for therapeutic intervention including the repurposing of current drugs.

Competition Between Two Excitation-dissociation Channels for Molecular Ions

When the molecular ions XYZ＋ （XY2＋） are excited simultaneously from an electronic state E0 into two higher electronic states Ea and EZ with supervened dissociation or predisso- ciation, competition between the α and β excitation-dissociation channels occurs. A the- oretical model is provided to deal with the competition of the two excitation-dissociation channels with more than two kinds of ionic products for XYZ＋ （XY2＋）. Supposing that the photo-excitation rates of two states Eα and Eβ are much less than their dissociation or pre-dissociation rates, a theoretical equation can be deduced to fit the measured data, which reflects the dependence of the product branching ratios on the intensity ratios of two excitation lasers. From the fitted parameters the excitation cross section ratios are obtained. In experiment, we studied the competition between two excitation-dissociation channels of CO^2＋. By measuring the dependence of the product branching ratio on the intensity ratio of two dissociation lasers and fitting the experiment data with the theoretical equation, excitation cross section ratios were deduced.

PIC simulation of plasma properties in the discharge channel of a pulsed plasma thruster with flared electrodes

Plasma in the discharge channel of a pulsed plasma thruster(PPT) with flared electrodes is simulated by a self-developed two-dimensional code. The fully particle-in-cell method with Monte Carlo collision is employed to model the particle movement and collisions and investigate the plasma properties and acceleration process. Temporal and spatial variations of the electron density distribution and the ion velocity between electrodes are calculated and analyzed in detail.The computational results of the electron number density, which is in the order of 1023 m-3,show good agreements with experimental results of a PPT named ADD SIMP-LEX. The ion velocity distributions along the center line of the channel lead to a comprehensive understanding of ions accelerated by electromagnetic field. The electron distributions of PPT with discharge voltages varying from 1300 to 2000 V are compared. The diffusion of electrons presents strong dependency on discharge voltage and implies higher degree of ionization for higher voltage.

Regulating effect of Tong Xie-Yao Fang on colonic epithelial secretion via Cl- and HCO3- channel

AIM To investigate the pharmacological effect of Tong XieYao Fang(TXYF) formula, a Chinese herbal formula, on Diarrhea-predominant irritable bowel syndrome(D-IBS) rats.METHODS In a neonatal maternal separation plus restraint stress(NMS + RS) model of D-IBS, male Sprague Dawley rats were randomly divided into two groups(NMS + RS group and TXYF-formula group) with no handlings were used as controls(NH group). Starting from postnatalday 60, rats in TXYF-formula group were administered TXYF-formula(4.92 g/100 g bodyweight) orally twice a day for 14 consecutive days while NH group and NMS + RS group were given distilled water. Using short-circuit current technology, we observed 5-HT-induced changes of current across ion channels, such as cystic fibrosis transmembrane conductance regulator(CFTR) Clchannel, epithelial Na+ channel(ENaC), Ca2+-dependent Cl- channel(CACC), Na+-K+-2Cl- co-transporter(NKCC), and Na+-HCO-3 co-transporter(NBC), in the colonic epithelium of three groups after exposure to drugs and specific blockers with a Power Lab System(AD Instruments International).RESULTS Under basal conditions, the changes of short-circuit current(?Isc, μA/cm2) induced by 5-HT were similar in NH group and TXYF-formula group, and both higher than NMS + RS group(70.86 μA/cm2 ± 12.32 μA/cm2, 67.67 μA/cm2 ± 11.68 μA/cm2 vs 38.8 μA/cm2 ± 7.25 μA/cm2, P < 0.01, respectively). When CACC was blocked by 4,4′-diisothiocyanato-stilbene-2,2′-disulfonic acid, 5-HT-induced ?Isc was smaller in NMS + RS group than in NH group and TXYF-formula group, respectively(48.41 μA/cm2 ± 13.15 μA/cm2 vs 74.62 μA/cm2 ± 10.73 μA/cm2, 69.22 μA/cm2 ± 11.7 μA/cm2, P < 0.05, respectively). The similar result could be obtained when ENaC was blocked by Amiloride(44.69 μA/cm2 ± 12.58 μA/cm2 vs 62.05 μA/cm2 ± 11.26 μA/cm2, 62.11 μA/cm2 ± 12.01 μA/cm2, P < 0.05, respectively). However, when CFTR Cl- channel was blocked by 1,1-dimethyl piperidinium chloride(DPC), 5-HT-induced ?Isc did not significantly differ in three groups(42.28 μA/cm2 ± 10.61 μA/cm2 vs 51.48 μA/cm2 ± 6.56 μA/cm2 vs 47.75 μA/cm2 ± 7.99 μA/cm2, P > 0.05, respectively). The similar results could also be obtained in three groups when NBC and NKCC were respectively blocked by their blockers.CONCLUSION TXYF-formula can regulate the Cl- and HCO-3 secretion of colonic mucosa via CFTR Cl- channel, Cl-/HCO-3 exchanger, NBC and NKCC co-transporters.

Diabetes-induced changes in cardiac voltage-gated ion channels

Diabetes mellitus affects the heart through various mechanisms such as microvascular defects,metabolic abnormalities,autonomic dysfunction and incompatible immune response.Furthermore,it can also cause functional and structural changes in the myocardium by a disease known as diabetic cardiomyopathy(DCM)in the absence of coronary artery disease.As DCM progresses it causes electrical remodeling of the heart,left ventricular dysfunction and heart failure.Electrophysiological changes in the diabetic heart contribute significantly to the incidence of arrhythmias and sudden cardiac death in diabetes mellitus patients.In recent studies,significant changes in repolarizing K+currents,Na+currents and L-type Ca^(2+)currents along with impaired Ca^(2+ )homeostasis and defective contractile function have been identified in the diabetic heart.In addition,insulin levels and other trophic factors change significantly to maintain the ionic channel expression in diabetic patients.There are many diagnostic tools and management options for DCM,but it is difficult to detect its development and to effectively prevent its progress.In this review,diabetes-associated alterations in voltage-sensitive cardiac ion channels are comprehensively assessed to understand their potential role in the pathophysiology and pathogenesis of DCM.

Differential Effect of Calcium-Activated Potassium and Chloride Channels on Rat Basilar Artery Vasomotion

Spontaneous, rhythmical contractions, or vasomotion, can be recorded from cerebral vessels under both normal physiological and pathophysiological conditions. We investigated the cellular mechanisms underlying vasomotion in the cerebral basilar artery （BA） of Wistar rats. Pressure myograph video microscopy was used to study the changes in cerebral artery vessel diameter. The main results of this study were as follows： （1） The diameters of BA and middle cerebral artery （MCA） were 314.5±15.7 μm （n=15） and 233.3±10.1 μm （n=12） at 10 mmHg working pressure （P〈0.05）, respectively. Pressure-induced vasomotion occurred in BA （22/28, 78.6%）, but not in MCA （4/31, 12.9%） from 0 to 70 mmHg working pressure. As is typical for vasomotion, the contractile phase of the response was more rapid than the relaxation phase; （2） The frequency of vasomotion response and the diameter were gradually increased in BA from 0 to 70 mmHg working pressure. The amplitude of the rhythmic con- tractions was relatively constant once stable conditions were achieved. The frequency of contractions was variable and the highest value was 16.7±4.7 （n=13） per 10 min at 60 mmHg working pressure; （3） The pressure-induced vasomotion of the isolated BA was attenuated by nifedipine, NFA, 181]-GA, TEA or in Ca2＋-free medium. Nifedipine, NFA, 18^-GA or Ca2＋-free medium not only dampened vasomotion, but also kept BA in relaxation state. In contrasts, TEA kept BA in contraction state. These results sug- gest that the pressure-induced vasomotion of the isolated BA results from an interaction between Ca2＋-activated C1- channels （CaCCs） currents and Kca currents. We hypothesize that vasomotion of BA depends on the depolarizing of the vascular smooth muscle cells （VSMCs） to activate CaCCs. Depolarization in turn activates voltage-dependent Ca2＋ channels, synchronizing contractions of adjacent cells through influx of extracellular calcium and the flow of calcium through gap junctions. Subsequent calcium-induced calcium release from ryanodine-sensitive stores activates Kca channels and hyperpo- larizes VSMCs, which provides a negative feedback loop for regenerating the contractile cycle.

General anesthesia mediated by effects on ion channels

Although it has been more than 165 years since the first introduction of modern anesthesia to the clinic, there is surprisingly little understanding about the exact mechanisms by which general anesthetics induce unconsciousness. As a result, we do not know how general anesthetics produce anesthesia at different levels. The main handicap to understanding the mechanisms of general anesthesia is the diversity of chemically unrelated compounds including diethyl ether and halogenated hydrocarbons, gases nitrous oxide, ketamine, propofol, benzodiazepines and etomidate, as well as alcohols and barbiturates. Does this imply that general anesthesia is caused by many different mechanisms? Until now, many receptors, molecular targets and neuronal transmission pathways have been shown to contribute to mechanisms of general anesthesia. Among these molecular targets, ion channels are the most likely candidates for general anesthesia, in particular γ-aminobutyric acid type A, potassium and sodium channels, as well as ion channels mediated by various neuronal transmitters like acetylcholine, amino acids amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid or N-methyl-D-aspartate. In addition, recent studies have demonstrated the involvement in general anesthesia of other ion channels with distinct gating properties suchas hyperpolarization-activated, cyclic- nucleotide-gated channels. The main aim of the present review is to summarize some aspects of current knowledge of the effects of general anesthetics on various ion channels.

Identification and Function of Acid-sensing Ion Channels in RAW 264.7 Macrophage Cells

Activation of acid-sensing ion channels （ASICs） plays an important role in neuroinflammation. Macrophage recruitment to the sites of inflammation is an essential step in host defense. ASIC1 and ASIC3 have been reported to mediate the endocytosis and maturation of bone marrow derived macrophages. However, the expression and inflammation-related functions of ASICs in RAW 264.7 cells, another common macrophage, are still elusive. In the present study, we first demonstrated the presence of ASIC 1, ASIC2a and ASIC3 in RAW 264.7 macrophage cell line by using reverse transcriptase polymerase chain reaction （RT-PCR）, Western blotting and immunofluorescence experiments. The non-specific ASICs inhibitor amiloride and specific homomeric ASICla blocker PcTxl reduced the production of iNOS and COX-2 by LPS-induced activating RAW 264.7 cells. Furthermore, not only amiloride but also PcTxl inhibited the migration and LPS-induced apoptosis of RAW 264.7 cells. Taken together, our findings suggest that ASICs promote the inflammatory response and apoptosis of RAW 264.7 cells, and ASICs may serve as a potential novel target for immunological disease therapy.

Constructing an ion‐oriented channel on a zinc electrode through surface engineering

The inherent shortcomings of a zinc anode in aqueous zinc‐ion batteries(ZIBs)such as zinc dendrites and side reactions severely limit their practical application.Herein,to address these issues,an ion‐oriented transport channel constructed by graphdiyne(GDY)nanowalls is designed and grown in situ on the surface of a zinc electrode.The vertically stacked GDY nanowalls with a unique hierarchical porous structure and mechanical properties form a nanomesh‐like interface on the zinc electrode,acting as an ion‐oriented channel,which can efficiently confine the segmented growth of zinc metal in microscopic regions of hundreds of nanometers.In those microscopic regions,the uniform domain current density is effortlessly maintained compared with a large surface area,thereby inhibiting zinc dendrites effectively.Besides,due to the presence of the ion‐oriented channel,the modified zinc anode demonstrates long‐term stable zinc plating/stripping performance for more than 600 h at 1 mAh cm^(−2)in an aqueous electrolyte.In addition,full‐cells coupled with MnO2 show high specific capacity and power density,as well as excellent cycling stability with a capacity retention of 82%after 5000 cycles at 1 A g^(−1).This work provides a feasible and accessible surface engineering approach to modify the electrode interface for confined and dendrite‐free zinc deposition in aqueous ZIBs.

Expert consensus of the Chinese Association for the Study of Pain on ion channel drugs for neuropathic pain

Neuropathic pain(NPP)is a kind of pain caused by disease or damage impacting the somatosensory system.Ion channel drugs are the main treatment for NPP;however,their irregular usage leads to unsatisfactory pain relief.To regulate the treatment of NPP with ion channel drugs in clinical practice,the Chinese Association for the Study of Pain organized first-line pain management experts from China to write an expert consensus as the reference for the use of ion channels drugs.Here,we reviewed the mechanism and characteristics of sodium and calcium channel drugs,and developed recommendations for the therapeutic principles and clinical practice for carbamazepine,oxcarbazepine,lidocaine,bulleyaconitine A,pregabalin,and gabapentin.We hope this guideline provides guidance to clinicians and patients on the use of ion channel drugs for the management of NPP.

Basics on the use of acid-sensing ion channels' inhibitors as therapeutics

Since the discovery of acid-sensing ion channels in 1997, their importance in the health of neurons and other non-neuronal cells has gained significant importance. Acid-sensing ion channels play important roles in mediating pain sensation during diseases such as stroke, inflammation, arthritis, cancer, and recently migraine. More interestingly, acid-sensing ion channels may explain the sex differences in pain between males and females. Also, the ability of acid-sensing ion channel blockers to exert neuroprotective effects in a number of neurodegenerative diseases has added a new dimension to their therapeutic value. The current failure rate of ～45% of new drugs(due to toxicity issues) and saving of up to 7 years in the life span of drug approval makes drug repurposing a high priority. If acid-sensing ion channels' blockers undergo what is known as "drug repurposing", there is a great potential to bring them as medications with known safety profiles to new patient populations. However, the route of administration remains a big challenge due to their poor penetration of the blood brain and retinal barriers. In this review, the promise of using acid-sensing ion channel blockers as neuroprotective drugs is discussed.

Modulatory effects of the fruits of Tribulus terrestris L. on the function of atopic dermatitis-related calcium channels,Orai1 and TRPV3

Objective: To examine the effects of Tribulus terrestris L.(T. terrestris) extract on the modulation of calcium channels to evaluate its use in topical agents for treatment of atopic dermatitis.Methods: The 70% methanol extract of T. terrestris was prepared. Human HEK293 T cells with over-expressed calcium release-activated calcium channel protein 1(Orai1),transient receptor potential vanilloid 1, or transient receptor potential vanilloid 3(TRPV3)were treated with T. terrestris extract. Modulation of ion channels was measured using a conventional whole-cell patch-clamp technique.Results: T. terrestris extract(100 mg/m L) significantly inhibited Orai1 activity in Orai1-stromal interaction molecule 1 co-overexpressed HEK293 T cells. In addition, T. terrestris extract significantly increased the TRPV3 activity compared with 2-Aminoethyl diphenylborinate(100 mmol/L), which induces the full activation of TRPV3.Conclusions: Our results suggest that T. terrestris extract may have a therapeutic potential for recovery of abnormal skin barrier pathologies in atopic dermatitis through modulating the activities of calcium ion channels, Orai1 and TRPV3. This is the first study to report the modulatory effect of a medicinal plant on the function of ion channels in skin barrier.

Could non-invasive brain-stimulation prevent neuronal degeneration upon ion channel re-distribution and ion accumulation after demyelination?

Fast and efficient transmission of electrical signals in the nervous system is mediated through myelinated nerve fibers.In neuronal diseases such as multiple sclerosis,the conduction properties of axons are disturbed by the removal of the myelin sheath,leaving nerve cells at a higher risk of degenerating.In some cases,the protective myelin sheath of axons can be rebuilt by remyelination through oligodendroglial cells.In any case,however,changes in the ion channel organization occur and may help to restore impulse conduction after demyelination.On the other hand,changes in ion channel distribution may increase the energy demand of axons,thereby increasing the probability of axonal degeneration.Many attempts have been made or discussed in recent years to increase remyelination of affected axons in demyelinating diseases such as multiple sclerosis.These approaches range from pharmacological treatments that reduce inflammatory processes or block ion channels to the modulation of neuronal activity through electrical cortical stimulation.However,these treatments either affect the entire organism(pharmacological)or exert a very local effect(electrodes).Current results show that neuronal activity is a strong regulator of oligodendroglial development.To bridge the gap between global and very local treatments,non-invasive transcranial magnetic stimulation could be considered.Transcranial magnetic stimulation is externally applied to brain areas and experiments with repetitive transcranial magnetic stimulation show that the neuronal activity can be modulated depending on the stimulation parameters in both humans and animals.In this review,we discuss the possibilities of influencing ion channel distribution and increasing neuronal activity by transcranial magnetic stimulation as well as the effect of this modulation on oligodendroglial cells and their capacity to remyelinate previously demyelinated axons.Although the physiological mechanisms underlying the effects of transcranial magnetic stimulation clearly need further investigations,repetitive transcranial magnetic stimulation may be a promising approach for non-invasive neuronal modulation aiming at enhancing remyelination and thus reducing neurodegeneration.