Trafficking mechanisms underlying Nav channel subcellular localization in neurons.
Authors: Solé L, Tamkun MM Abstract Voltage gated sodium channels (Nav) play a crucial role in action potential initiation and propagation. Although the discovery of Nav channels dates back more than 65 years, and great advances in understanding their localization, biophysical properties, and links to disease have been made, there are still many questions to be answered regarding the cellular and molecular mechanisms involved in Nav channel trafficking, localization and regulation. This review summarizes the different trafficking mechanisms underlying the polarized Nav channel localization in neurons, w...
Source: Channels - December 18, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Bibliometric analysis of potassium channel research.
Authors: Shi J, Shi S, Shi S, Jia Q, Yuan G, Chu Y, Wang H, Hu Y, Cui H PMID: 31842669 [PubMed - as supplied by publisher] (Source: Channels)
Source: Channels - December 18, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Elementary calcium signaling in arterial smooth muscle.
Authors: Fan G, Cui Y, Gollasch M, Kassmann M Abstract Vascular smooth muscle cells (VSMCs) of small peripheral arteries contribute to blood pressure control by adapting their contractile state. These adaptations depend on the VSMC cytosolic Ca2+ concentration, regulated by complex local elementary Ca2+ signaling pathways. Ca2+ sparks represent local, transient, rapid calcium release events from a cluster of ryanodine receptors (RyRs) in the sarcoplasmic reticulum. In arterial SMCs, Ca2+ sparks activate nearby calcium-dependent potassium channels, cause membrane hyperpolarization and thus decrease the global intrac...
Source: Channels - December 6, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

PI3K α in cardioprotection: Cytoskeleton, late Na+ current, and mechanism of arrhythmias.
PI3Kα in cardioprotection: Cytoskeleton, late Na+ current, and mechanism of arrhythmias. Channels (Austin). 2019 Dec;13(1):520-532 Authors: Zhabyeyev P, Chen X, Vanhaesebroeck B, Oudit GY Abstract PI 3-kinase α (PI3Kα) is a lipid kinase that converts phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-triphosphate (PIP3). PI3Kα regulates a variety of cellular processes such as nutrient sensing, cell cycle, migration, and others. Heightened activity of PI3Kα in many types of cancer made it a prime oncology drug target, but also raises concerns of poss...
Source: Channels - December 4, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

A conserved arginine/lysine-based motif promotes ER export of KCNE1 and KCNE2 to regulate KCNQ1 channel activity.
Authors: Hu B, Zeng WP, Li X, Al-Sheikh U, Chen SY, Ding J Abstract KCNE β-subunits play critical roles in modulating cardiac voltage-gated potassium channels. Among them, KCNE1 associates with KCNQ1 channel to confer a slow-activated IKs current, while KCNE2 functions as a dominant negative modulator to suppress the current amplitude of KCNQ1. Any anomaly in these channels will lead to serious myocardial diseases, such as the long QT syndrome (LQTS). Trafficking defects of KCNE1 have been reported to account for the pathogenesis of LQT5. However, the molecular mechanisms underlying KCNE forward trafficki...
Source: Channels - November 6, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Evaluation of edonerpic maleate as a CRMP2 inhibitor for pain relief.
Authors: Moutal A, Shan Z, Miranda VG, François-Moutal L, Madura CL, Khanna M, Khanna R Abstract We have previously reported that the microtubule-associated collapsin response mediator protein 2 (CRMP2) is necessary for the expression of chronic pain. CRMP2 achieves this control of nociceptive signaling by virtue of its ability to regulate voltage-gated calcium and sodium channels. To date, however, no drugs exist that target CRMP2. Recently, the small molecule edonerpic maleate (1 -{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate), a candidate therapeutic for Alzheimer's disease was reported ...
Source: Channels - November 6, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Ion channels as potential redox sensors in lysosomes.
Authors: Yu J, Yang J Abstract Lysosomes are central organelles that recycle materials and energy to maintain intracellular homeostasis. Lysosomes are capable of sensing environmental cues such as nutrition to regulate their function accordingly. Whether lysosomes can sense redox signaling, however, was unclear. Here in this review, we summarized recent evidence of lysosomal ion channel as redox sensors for this organelle. We also discussed their roles in lysosomal diseases that features imbalanced redox. PMID: 31662029 [PubMed - in process] (Source: Channels)
Source: Channels - November 1, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Voltage vs. Ligand I: Structural basis of the intrinsic flexibility of S3 segment and its significance in ion channel activation.
Authors: Balleza D, Rosas ME, Romero-Romero S Abstract We systematically predict the internal flexibility of the S3 segment, one of the most mobile elements in the voltage-sensor domain. By analyzing the primary amino acid sequences of V-sensor containing proteins, including Hv1, TPC channels and the voltage-sensing phosphatases, we established correlations between the local flexibility and modes of activation for different members of the VGIC superfamily. Taking advantage of the structural information available, we also assessed structural aspects to understand the role played by the flexibility of S3 during the g...
Source: Channels - October 27, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Anterograde trafficking signals in GABAA subunits are required for functional expression.
Authors: Nuwer JL, Fleck MW Abstract Pentameric GABAA receptors are composed from 19 possible subunits. The GABAA β subunit is unique because the β1 and β3 subunits can assemble and traffic to the cell surface as homomers, whereas most of the other subunits, including β2, are heteromers. The intracellular domain (ICD) of the GABAA subunits has been implicated in targeting and clustering GABAA receptors at the plasma membrane. Here, we sought to test whether and how the ICD is involved in functional expression of the β3 subunit. Since θ is the most homologous to β but does not for...
Source: Channels - October 17, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

The influence of membrane bilayer thickness on KcsA channel activity.
Authors: Callahan KM, Mondou B, Sasseville L, Schwartz JL, D'Avanzo N Abstract Atomic resolution structures have provided significant insight into the gating and permeation mechanisms of various ion channels, including potassium channels. However, ion channels may also be regulated by numerous factors, including the physiochemical properties of the membrane in which they are embedded. For example, the matching of the bilayer's hydrophobic region to the hydrophobic external surface of the ion channel is thought to minimize the energetic penalty needed to solvate hydrophobic residues or exposed lipid tails. To unders...
Source: Channels - October 15, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Heteromeric TRPV4/TRPC1 channels mediate calcium-sensing receptor-induced relaxations and nitric oxide production in mesenteric arteries: comparative study using wild-type and TRPC1-/- mice.
This study also suggests that heteromeric TRPV4-TRPC1 channels may form the predominant TRPV4-containing channels in mouse mesenteric artery ECs. Together, our data further implicates CaSR-induced pathways and heteromeric TRPV4/TRPC1 channels in the regulation of vascular tone. PMID: 31603369 [PubMed - as supplied by publisher] (Source: Channels)
Source: Channels - October 12, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Voltage vs. Ligand II: Structural insights of the intrinsic flexibility in cyclic nucleotide-gated channels.
In this study, we describe in detail the flexibility profile of the voltage-sensor domain (VSD) and the pore domain (PD) concerning the evolution of 6TM ion channels. In particular, we highlight the role of flexibility in the emergence of CNG channels and describe a significant level of sequence similarity between the archetypical VSD and the TolQ proteins. A highly flexible S4-like segment exhibiting Lys instead Arg for these membrane proteins is reported. Sequence analysis indicates that, in addition to this S4-like segment, TolQ proteins also show similarity with specific motifs in S2 and S3 from typical V-sensors. Nota...
Source: Channels - September 27, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

TRPML1 and RAS-driven cancers - exploring a link with great therapeutic potential.
Authors: Jung J, Venkatachalam K Abstract Activating mutations in the RAS family of proto-oncogenes represent some of the leading causes of cancer. Unmitigated proliferation of cells harboring oncogenic RAS mutations is accompanied by a massive increase in cellular bioenergetic demands, which offers unique opportunities for therapeutic intervention. To withstand the steep requirements for metabolic intermediates, RAS-driven cancer cells enhance endolysosome and autophagosome biogenesis. By degrading cellular macromolecules into metabolites that can be used by biosynthetic pathways, endolysosomes permit continued pr...
Source: Channels - September 20, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Acid-sensing ion channels mediate the degeneration of intervertebral disc via various pathways-A systematic review.
Authors: Guo Y, Meng Y, Liu H, Wang B, Ding C, Rong X, Yang Y, Hong Y Abstract To elucidate the pathological significance of acid-sensing ion channels (ASICs) in intervertebral disc degeneration (IVDD), the database of Medline, Web of Science, and EmBase were carefully screened. Search terms used in each database varied slightly to optimize results. Data relating to the correlation between ASICs and IVDD was systematically collected and integrated into the review. 11 basic science studies, containing the related information, were finally identified for inclusion. Intervertebral disc degeneration (IVDD) is a common ...
Source: Channels - September 20, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Voltage Gated Sodium Channels in Cancer and Their Potential Mechanisms of Action.
Authors: Angus M, Ruben P Abstract Voltage gated sodium channels (VGSC) are implicated in cancer cell invasion and metastasis. However, the mechanism by which VGSC increase cell invasiveness and probability of metastasis is still unknown. In this review we outline lesser known functions of VGSC outside of action potential propagation, and the current understanding of the effects of VGSC in cancer. Finally, we discuss possible downstream effects of VGSC activation in cancer cells. After extensive review of the literature, the most likely role of VGSC in cancer is in the invadopodia, the leading edge of metastatic ca...
Source: Channels - September 14, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Myrcene and terpene regulation of TRPV1.
Authors: Jansen C, Shimoda LMN, Kawakami JK, Ang L, Bacani AJ, Baker JD, Badowski C, Speck M, Stokes AJ, Small-Howard AL, Turner H Abstract Nociceptive Transient Receptor Potential channels such as TRPV1 are targets for treating pain. Both antagonism and agonism of TRP channels can promote analgesia, through inactivation and chronic desensitization. Since plant-derived mixtures of cannabinoids and the Cannabis component myrcene have been suggested as pain therapeutics, we screened terpenes found in Cannabis for activity at TRPV1. We used inducible expression of TRPV1 to examine TRPV1-dependency of terpene-induced c...
Source: Channels - August 28, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Role of the voltage sensor module in Nav domain Ⅳ on fast inactivation in sodium channelopathies: The implication of closed-state inactivation.
Authors: Nakajima T, Kaneko Y, Dharmawan T, Kurabayashi M Abstract The segment 4 (S4) voltage sensor in voltage-gated sodium channels (Navs) have domain-specific functions, and the S4 segment in domain DⅣ (DⅣS4) plays a key role in the activation and fast inactivation processes through the coupling of arginine residues in DⅣS4 with residues of putative gating charge transfer center (pGCTC) in DⅣS1-3. In addition, the first four arginine residues (R1-R4) in Nav DⅣS4 have position-specific functions in the fast inactivation process, and mutations in these residues are associated with diverse phenotypes of N...
Source: Channels - August 1, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Silencing of KCNA1 suppresses the cervical cancer development via mitochondria damage.
This study aimed to identify the role of KCNA1 in cervical cancer and explore the related mechanism. The levels of KCNA1 in cervical cancer tissues and cell lines were examined by Western blot and qPCR. Cell proliferation and invasion were assessed by CCK-8 and transwell assays, respectively. Protein levels of Hedgehog (Hhg), Wnt and Notch were detected by Western blot. The mitochondrial capacity was examined by immunostaining with MitoTracker Red CMXRos. KCNA1 was highly expressed in cervical cancer tissues and cell lines, and correlated with poor prognosis. In addition, depletion of KCNA1 suppressed growth, proliferation...
Source: Channels - July 30, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

No transcriptional evidence for active Nav channels in two classes of cancer cell.
In this study, the transcriptional consequences of channel inhibition were investigated in non-small cell lung carcinoma H460 and neuroblastoma SH-SYSY cell lines, that both express Nav1.7. Channel activity was blocked by the application of both selective, ProTx-II, and non-selective, tetrodotoxin, inhibitors. Global gene expression profiling did not point to any statistically significant inhibition-associated perturbation of the transcriptome. A small subset of genes that showed relatively consistent changes across multiple treatments were further assayed in the context of a multiplex bead expression array which failed to...
Source: Channels - July 23, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

SCN5A mutation G615E results in NaV1.5 voltage-gated sodium channels with normal voltage-dependent function yet loss of mechanosensitivity.
Authors: Strege PR, Mercado-Perez A, Mazzone A, Saito YA, Bernard CE, Farrugia G, Beyder A Abstract SCN5A is expressed in cardiomyocytes and gastrointestinal (GI) smooth muscle cells (SMCs) as the voltage-gated mechanosensitive sodium channel NaV1.5. The influx of Na+ through NaV1.5 produces a fast depolarization in membrane potential, indispensable for electrical excitability in cardiomyocytes and important for electrical slow waves in GI smooth muscle. As such, abnormal NaV1.5 voltage gating or mechanosensitivity may result in channelopathies. SCN5A mutation G615E - found separately in cases of acquired long-QT s...
Source: Channels - July 3, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

pHluorin-tagged TRPV1 shines light on capsaicin tachyphylaxis.
Authors: Agosti F, Altier C PMID: 31262222 [PubMed - as supplied by publisher] (Source: Channels)
Source: Channels - July 3, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Kv1.1 channel subunits in the control of neurocardiac function.
Authors: Glasscock E Abstract Voltage-gated Kv1.1 potassium channel α-subunits are broadly expressed in the nervous system where they act as critical regulators of neuronal excitability. Mutations in the KCNA1 gene, which encodes Kv1.1, are associated with the neurological diseases episodic ataxia and epilepsy. Studies in mouse models have shown that Kv1.1 is important for neural control of the heart and that Kcna1 deletion leads to cardiac dysfunction that appears to be brain-driven. Traditionally, KCNA1 was not believed to be expressed in the heart. However, recent studies have revealed that Kv1.1 subunits ...
Source: Channels - June 30, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

In vitro exposure to Hymenoptera venom and constituents activates discrete ionotropic pathways in mast cells.
Authors: Jansen C, Shimoda LMN, Starkus J, Lange I, Rysavy N, Maaetoft-Udsen K, Tobita C, Stokes AJ, Turner H Abstract Calcium entry is central to the functional processes in mast cells and basophils that contribute to the induction and maintenance of inflammatory responses. Mast cells and basophils express an array of calcium channels, which mediate responses to diverse stimuli triggered by small bioactive molecules, physicochemical stimuli and immunological inputs including antigens and direct immune cell interactions. These cells are also highly responsive to certain venoms (such as Hymenoptera envenomations), w...
Source: Channels - June 27, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

The role of oligodendrocyte gap junctions in neuroinflammation.
Authors: Papaneophytou C, Georgiou E, Kleopa KA Abstract Gap junctions (GJs) provide channels for direct cell-to-cell connectivity serving the homeostasis in several organs of vertebrates including the central (CNS) and peripheral (PNS) nervous systems. GJs are composed of connexins (Cx), which show a highly distinct cellular and subcellular expression pattern. Oligodendrocytes, the myelinating cells of the CNS, are characterized by extensive GJ connectivity with each other as well as with astrocytes. The main oligodendrocyte connexins forming these GJ channels are Cx47 and Cx32. The importance of these channels ha...
Source: Channels - June 26, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Airway regeneration using iPS cell-derived airway epithelial cells with Cl- channel function.
Authors: Yoshie S, Omori K, Hazama A Abstract induced pluripotent stem (iPS) cells can be differentiated into various cell types, including airway epithelial cells, since they have the capacity for self-renewal and pluripotency. Thus, airway epithelial cells generated from iPS cells are expected to be potent candidates for use in airway regeneration and the treatment of airway diseases such as cystic fibrosis (CF). Recently, it was reported that iPS cells can be differentiated into airway epithelial cells according to the airway developmental process. These studies demonstrate that airway epithelial cells generated...
Source: Channels - June 16, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

The potential role of TRPV1 in pulmonary hypertension: angel or demon?
Authors: Zhang X, Ye L, Huang Y, Ding X, Wang L Abstract Pulmonary hypertension (PH) is a pathological state defined by increased pulmonary artery pressure, the pathogenesis of which is related to genetic mutations, intracellular calcium ([Ca2+]i), inflammation and proliferation. Transient receptor potential vanilloid subfamily member 1 (TRPV1) is a nonselective cation channel expressed in neural and nonneural cells, including pulmonary vessels and nerves. As a calcium channel, TRPV1 can make vessels contracted, and promote smooth muscle cells proliferation through calcium-dependent transcription factors. Activatio...
Source: Channels - June 15, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

TRP ion channels: Proteins with conformational flexibility.
Authors: López-Romero AE, Hernández-Araiza I, Torres-Quiroz F, Tovar-Y-Romo LB, Islas LD, Rosenbaum T Abstract Ion channels display conformational changes in response to binding of their agonists and antagonists. The study of the relationships between the structure and the function of these proteins has witnessed considerable advances in the last two decades using a combination of techniques, which include electrophysiology, optical approaches (i.e. patch clamp fluorometry, incorporation of non-canonic amino acids, etc.), molecular biology (mutations in different regions of ion channels to determine t...
Source: Channels - June 13, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Stimulation of TRPA1 attenuates ischemia-induced cardiomyocyte cell death through an eNOS-mediated mechanism.
Authors: Andrei SR, Ghosh M, Sinharoy P, Damron DS Abstract The functional expression of transient receptor potential cation channel of the ankyrin-1 subtype (TRPA1) has recently been identified in adult mouse cardiac tissue where stimulation of this ion channel leads to increases in adult mouse ventricular cardiomyocyte (CM) contractile function via a Ca2+-Calmodulin-dependent kinase (CaMKII) pathway. However, the extent to which TRPA1 induces nitric oxide (NO) production in CMs, and whether this signaling cascade mediates physiological or pathophysiological events in cardiac tissue remains elusive. Freshly isolat...
Source: Channels - June 6, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Mechano-electrical transduction in trabecular meshwork involves parallel activation of TRPV4 and TREK-1 channels.
Authors: Yarishkin O, Baumann JM, Križaj D PMID: 31161865 [PubMed - in process] (Source: Channels)
Source: Channels - June 6, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Diverse TRPV1 responses to cannabinoids.
Authors: Starkus J, Jansen C, Shimoda LMN, Stokes AJ, Small-Howard AL, Turner H Abstract Cannabinoid compounds are potential analgesics. Users of medicinal Cannabis report efficacy for pain control, clinical studies show that cannabis can be effective and opioid sparing in chronic pain, and some constituent cannabinoids have been shown to target nociceptive ion channels. Here, we explore and compare a suite of cannabinoids for their impact upon the physiology of TRPV1. The cannabinoids tested evoke differential responses in terms of kinetics of activation and inactivation. Cannabinoid activation of TRPV1 displays s...
Source: Channels - May 19, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Cannabinoid interactions with ion channels and receptors.
Authors: Watkins AR Abstract Cannabidiol (CBD), the non-psychoactive component of Cannabis sativa, acts on a diverse selection of membrane proteins with promising therapeutic potential in epilepsy and chronic pain. One such protein is the voltage-gated sodium channel (Nav). CBD shows a lack of specificity for sodium channels; however, the method of interaction is still unknown. In this review, we will outline the studies that report reproducible results of CBD and other cannabinoids changing membrane channel function, with particular interest on Nav. Nav are implicated in fatal forms of epilepsy and are also associ...
Source: Channels - May 17, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Compound heterozygous CACNA1H mutations associated with severe congenital amyotrophy.
Authors: Carter MT, McMillan HJ, Tomin A, Weiss N Abstract Neuromuscular disorders encompass a wide range of conditions often associated with a genetic component. In the present study, we report a patient with severe infantile-onset amyotrophy in whom two compound heterozygous variants in the gene CACNA1H encoding for Cav3.2 T-type calcium channels were identified. Functional analysis of Cav3.2 variants revealed several alterations of the gating properties of the channel that were in general consistent with a loss-of-channel function. Taken together, these findings suggest that severe congenital amyoplasia may be r...
Source: Channels - May 10, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Comparative docking analysis of cholesterol analogs to ion channels to discriminate between stereospecific binding vs. stereospecific response.
In this study, we challenge this paradigm by docking analyses of cholesterol and its chiral isomers to five ion channels whose response to cholesterol was shown to be stereospecific, Kir2.2, KirBac1.1, TRPV1, GABAA and BK. The analysis is performed using AutoDock Vina to predict the binding poses and energies of the sterols to the channels and identify amino acids interacting with the sterol molecules. We found that for every ion channel tested herein all three sterols showed similar binding poses and significant overlap in the set of the amino acids that comprise the predicted binding sites, along with similar energetic f...
Source: Channels - April 30, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Activity of T-type calcium channels is independent of CRMP2 in sensory neurons.
Authors: Cai S, Shan Z, Zhang Z, Moutal A, Khanna R Abstract Amongst the regulators of voltage-gated ion channels is the collapsin response mediator protein 2 (CRMP2). CRMP2 regulation of the activity and trafficking of NaV1.7 voltage-gated sodium channels as well as the N-type (CaV2.2) voltage-gated calcium channel (VGCC) has been reported. On the other hand, CRMP2 does not appear to regulate L- (CaV1.x), P/Q- (CaV2.1), and R- (CaV2.3) type high VGCCs. Whether CRMP2 regulates low VGCCs remains an open question. Here, we asked if CRMP2 could regulate the low voltage-gated (T-type/CaV3.x) channels in sensory neurons...
Source: Channels - April 27, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

A small viral potassium ion channel with an inherent inward rectification.
Authors: Eckert D, Schulze T, Stahl J, Rauh O, Van Etten JL, Hertel B, Schroeder I, Moroni A, Thiel G Abstract Some algal viruses have coding sequences for proteins with structural and functional characteristics of pore modules of complex K+ channels. Here we exploit the structural diversity among these channel orthologs to discover new basic principles of structure/function correlates in K+ channels. The analysis of three similar K+ channels with ≤ 86 amino acids (AA) shows that one channel (Kmpv1) generates an ohmic conductance in HEK293 cells while the other two (KmpvSP1, KmpvPL1) exhibit typical features of ...
Source: Channels - April 24, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

CACHD1: A new activity-modifying protein for voltage-gated calcium channels.
Authors: Stephens GJ, Cottrell GS PMID: 30983497 [PubMed - in process] (Source: Channels)
Source: Channels - April 19, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Overlap of periodic paralysis and paramyotonia congenita caused by SCN4A gene mutations.
Conclusions SCN4A gene mutations can cause the overlap of PMC and PP (especially the HypoPP2). The clinical symptoms of episodic weakness and stiffness could happen at the different time or temperature. Based on diagnosis assessments such as medical history and muscle biopsy, further evaluations on long-time exercise test, genetic analysis and patch clamp electrophysiology test need to be done in order to verify the specific subtype of channelopathies. Furthermore, the improvement of one member in pregnancy period can be used as a reference for the other female in child-bearing period with T704M. PMID: 30931713 [PubMed...
Source: Channels - April 3, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Fluorescence microscopy of piezo1 in droplet hydrogel bilayers.
Authors: Jaggers OB, Ridone P, Martinac B, Baker MAB Abstract Mechanosensitive ion channels are membrane gated pores which are activated by mechanical stimuli. The focus of this study is on Piezo1, a newly discovered, large, mammalian, mechanosensitive ion channel, which has been linked to diseases such as dehydrated hereditary stomatocytosis (Xerocytosis) and lymphatic dysplasia. Here we utilize an established in-vitro artificial bilayer system to interrogate single Piezo1 channel activity. The droplet-hydrogel bilayer (DHB) system uniquely allows the simultaneous recording of electrical activity and fluorescence ...
Source: Channels - March 21, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Kv2 channels create endoplasmic reticulum / plasma membrane junctions: a brief history of Kv2 channel subcellular localization.
Authors: Johnson B, Leek AN, Tamkun MM Abstract The potassium channels Kv2.1 and Kv2.2 are widely expressed throughout the mammalian brain. Kv2.1 provides the majority of delayed rectifying current in rat hippocampus while both channels are differentially expressed in cortex. Particularly unusual is their neuronal surface localization pattern: while half the channel population is freely-diffusive on the plasma membrane as expected from the generalized Singer & Nicolson fluid mosaic model, the other half localizes into micron-sized clusters on the soma, dendrites, and axon initial segment. These clusters contain...
Source: Channels - February 5, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Regional differences in the expression of tetrodotoxin-sensitive inward Ca2+ and outward Cs+/K+ currents in mouse and human ventricles.
Authors: Wang W, Mellor RL, Nerbonne JM, Balke CW Abstract Tetrodotoxin (TTX) sensitive inward Ca2+ currents, ICa(TTX), have been identified in cardiac myocytes from several species, although it is unclear if ICa(TTX) is expressed in all cardiac cell types, and if ICa(TTX) reflects Ca2+ entry through the main, Nav1.5-encoded, cardiac Na+ (Nav) channels. To address these questions, recordings were obtained with 2 mm Ca2+ and 0 mm Na+ in the bath and 120 mm Cs+ in the pipettes from myocytes isolated from adult mouse interventricular septum (IVS), left ventricular (LV) endocardium, apex, and epicardium and from human ...
Source: Channels - February 4, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Lifting the veils on TMEM16E function.
Authors: Boccaccio A, Di Zanni E, Gradogna A, Scholz-Starke J PMID: 30672373 [PubMed - in process] (Source: Channels)
Source: Channels - January 25, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Inhibition of multiple voltage-gated calcium channels may contribute to spinally mediated analgesia by epipregnanolone in a rat model of surgical paw incision.
Authors: Joksimovic SL, Donald RR, Park JY, Todorovic SM Abstract Voltage-activated calcium channels play an important role in excitability of sensory nociceptive neurons in acute and chronic pain models. We have previously shown that low-voltage-activated calcium channels, or T-type channels (T-channels), increase excitability of sensory neurons after surgical incision in rats. We have also found that endogenous 5β-reduced neuroactive steroid epipregnanolone [(3β,5β)-3-hydroxypregnan-20-one] blocked isolated T-currents in dorsal root ganglion (DRG) cells in vitro, and reduced nociceptive behavior in...
Source: Channels - January 25, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Arachidonic acid hyperpolarizes mesenchymal stromal cells from the human adipose tissue by stimulating TREK1 K+ channels.
Authors: Tarasov MV, Kotova PD, Bystrova MF, Kabanova NV, Sysoeva VY, Kolesnikov SS Abstract The current knowledge of electrogenesis in mesenchymal stromal cells (MSCs) remains scarce. Earlier, we demonstrated that in MSCs from the human adipose tissue, transduction of certain agonists involved the phosphoinositide cascade. Its pivotal effector PLC generates DAG that can regulate ion channels directly or via its derivatives, including arachidonic acid (AA). Here we showed that AA strongly hyperpolarized MSCs by stimulating instantly activating, outwardly rectifying TEA-insensitive K+ channels. Among AA-regulated K+...
Source: Channels - January 23, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Correcting the R165K substitution in the first voltage-sensor of CaV1.1 right-shifts the voltage-dependence of skeletal muscle calcium channel activation.
Authors: El Ghaleb Y, Campiglio M, Flucher BE Abstract The voltage-gated calcium channel CaV1.1a primarily functions as voltage-sensor in skeletal muscle excitation-contraction (EC) coupling. In embryonic muscle the splice variant CaV1.1e, which lacks exon 29, additionally function as a genuine L-type calcium channel. Because previous work in most laboratories used a CaV1.1 expression plasmid containing a single amino acid substitution (R165K) of a critical gating charge in the first voltage-sensing domain (VSD), we corrected this substitution and analyzed its effects on the gating properties of the L-type calcium ...
Source: Channels - January 16, 2019 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Rectification ratio based determination of disulfide bonds of β2 extracellular loop of BK channel.
Rectification ratio based determination of disulfide bonds of β2 extracellular loop of BK channel. Channels (Austin). 2018 Nov 26;: Authors: Guo X, Liu H, Huang Z, Wang Y, Zhang Y, Wang LY, Cao C, Wang S, Ding J Abstract Large-conductance Ca2+-activated K+ (BK) channels are composed of a pore-forming α and a variable number of auxiliary β subunits and play important roles in regulating excitability, action potential waveforms and firing patterns, particularly in neurons and endocrine and cardiovascular cells. The β2 subunits increase the diversity of gating and pharmacological prop...
Source: Channels - November 29, 2018 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Gating defects of disease-causing de novo mutations in Cav1.3 Ca2+ channels.
Authors: Pinggera A, Negro G, Tuluc P, Brown MJ, Lieb A, Striessnig J Abstract Recently, we and others identified somatic and germline de novo gain-of-function mutations in CACNA1D, the gene encoding the α1-subunit of voltage-gated Cav1.3 Ca2+-channels. While somatic mutations identified in aldosterone producing adenomas (APAs) underlie treatment-resistant hypertension, germline CACNA1D mutations are associated with a neurodevelopmental disorder characterized by a wide symptomatic spectrum, including autism spectrum disorder. The number of newly identified CACNA1D missense mutations is constantly growing, but...
Source: Channels - November 23, 2018 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

"TRPV1 is a component of the atrial natriuretic signaling complex, and using orally delivered antagonists, presents a valid therapeutic target in the longitudinal reversal and treatment of cardiac hypertrophy and heart failure".
Conclusions TRPV1 is a physical and regulated component of the natriuretic peptide signaling system, and TRPV1 inhibition may provide a new treatment strategy for treating the loss of function associated with cardiac hypertrophy and remodeling. PMID: 30424709 [PubMed - as supplied by publisher] (Source: Channels)
Source: Channels - November 16, 2018 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Role of individual S4 segments in gating of Cav3.1 T-type calcium channel by voltage.
Authors: Tarabova BJ, Mackova K, Moravcikova L, Karmazinova M, Lacinova L Abstract Contributions of voltage sensing S4 segments in domains I - IV of CaV3.1 channel to channel activation were analyzed. Neutralization of the uppermost charge in individual S4 segments by exchange of arginine for cysteine was employed. Mutant channels with single exchange in domains I -IV, in two adjacent domains, and in all four domains were constructed and expressed in HEK 293 cells. Changes in maximal gating charge Qmax and the relation between Qmax and maximal conductance Gmax were evaluated. Qmax was the most affected by single mu...
Source: Channels - November 9, 2018 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Effects of Acidosis on Neuronal Voltage-Gated Sodium Channels: Nav1.1 and Nav1.3.
In this study, we sought to determine whether Nav1.1 and Nav1.3 display resistance or sensitivity to changes in extracellular pH. These two sodium channel subtypes are predominantly found in inhibitory neurons. The expression of these channels highly depends on age and the developmental stage of neurons, with Nav1.3 being found mostly in neonatal neurons, and Nav1.1 being found in adult neurons. Our present results indicate that, during extracellular acidosis, both channels show a depolarization in the voltage-dependence of activation and moderate reduction in current density. Voltage-dependence of steady-state fast inacti...
Source: Channels - October 28, 2018 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Potassium channels in the sinoatrial node and their role in heart rate control.
Authors: Aziz Q, Li Y, Tinker A Abstract Potassium currents determine the resting membrane potential and govern repolarisation in cardiac myocytes. Here, we review the various currents in the sinoatrial node focussing on their molecular and cellular properties and their role in pacemaking and heart rate control. We also describe how our recent finding of a novel ATP-sensitive potassium channel population in these cells fits into this picture . PMID: 30301404 [PubMed - as supplied by publisher] (Source: Channels)
Source: Channels - October 13, 2018 Category: Molecular Biology Tags: Channels (Austin) Source Type: research