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Ion Channels

Javier Cervera, José A Manzanares, Salvador Mafe
Genetic networks operate in the presence of local heterogeneities in single-cell transcription and translation rates. Bioelectrical networks and spatio-temporal maps of cell electric potentials can influence multicellular ensembles. Could cell-cell bioelectrical interactions mediated by intercellular gap junctions contribute to the stabilization of multicellular states against local genetic heterogeneities? We theoretically analyze this question on the basis of two well-established experimental facts: (i) the membrane potential is a reliable read-out of the single-cell electrical state and (ii) when the cells are coupled together, their individual cell potentials can be influenced by ensemble-averaged electrical potentials...
March 22, 2018: Physical Chemistry Chemical Physics: PCCP
Mariana Alves, Edward Beamer, Tobias Engel
Epilepsy encompasses a heterogeneous group of neurological syndromes which are characterized by recurrent seizures affecting over 60 million people worldwide. Current anti-epileptic drugs (AEDs) are mainly designed to target ion channels and/or GABA or glutamate receptors. Despite recent advances in drug development, however, pharmacoresistance in epilepsy remains as high as 30%, suggesting the need for the development of new AEDs with a non-classical mechanism of action. Neuroinflammation is increasingly recognized as one of the key players in seizure generation and in the maintenance of the epileptic phenotype...
2018: Frontiers in Pharmacology
Samrat Thouta, Garman Lo, Lukas Grajauskas, Tom Claydon
The hERG channel is a key player in repolarization of the cardiac action potential. Pharmacological blockade of hERG channels depletes the cardiac repolarization reserve, increasing the risk of cardiac arrhythmias. The promiscuous nature of drug interactions with hERG presents a therapeutic challenge for drug design and development. Despite considerable effort, the mechanisms of drug binding remain incompletely understood. One proposed mechanism is that high-affinity drug binding preferentially occurs when channels are in the inactivated state...
March 21, 2018: Scientific Reports
Wojciech Leppert, Malgorzata Malec-Milewska, Renata Zajaczkowska, Jerzy Wordliczek
The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients' age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms...
March 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Ji She, Jiangtao Guo, Qingfeng Chen, Weizhong Zeng, Youxing Jiang, Xiao-Chen Bai
The organellar two-pore channel (TPC) functions as a homodimer, in which each subunit contains two homologous Shaker-like six-transmembrane (6-TM)-domain repeats. TPCs belong to the voltage-gated ion channel superfamily and are ubiquitously expressed in animals and plants. Mammalian TPC1 and TPC2 are localized at the endolysosomal membrane, and have critical roles in regulating the physiological functions of these acidic organelles. Here we present electron cryo-microscopy structures of mouse TPC1 (MmTPC1)-a voltage-dependent, phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2 )-activated Na+ -selective channel-in both the apo closed state and ligand-bound open state...
March 21, 2018: Nature
Tracey Ann Cuin, Ingo Dreyer, Erwan Michard
Fast responses to an external threat depend on the rapid transmission of signals through a plant. Action potentials (APs) are proposed as such signals. Plant APs share similarities with their animal counterparts; they are proposed to depend on the activity of voltage-gated ion channels. Nonetheless, despite their demonstrated role in (a)biotic stress responses, the identities of the associated voltage-gated channels and transporters remain undefined in higher plants. By demonstrating the role of two potassium-selective channels in Arabidopsis thaliana in AP generation and shaping, we show that the plant AP does depend on similar Kv -like transport systems to those of the animal signal...
March 21, 2018: International Journal of Molecular Sciences
Pradipta Ray, Andrew Torck, Lilyana Quigley, Andi Wangzhou, Matthew Neiman, Chandranshu Rao, Tiffany Lam, Ji-Young Kim, Tae Hoon Kim, Michael Q Zhang, Gregory Dussor, Theodore J Price
Molecular neurobiological insight into human nervous tissues is needed to generate next generation therapeutics for neurological disorders like chronic pain. We obtained human Dorsal Root Ganglia (DRG) samples from organ donors and performed RNA-sequencing (RNA-seq) to study the human DRG (hDRG) transcriptional landscape, systematically comparing it with publicly available data from a variety of human and orthologous mouse tissues, including mouse DRG (mDRG). We characterized the hDRG transcriptional profile in terms of tissue-restricted gene co-expression patterns and putative transcriptional regulators, and formulated an information-theoretic framework to quantify DRG enrichment...
March 20, 2018: Pain
Nicola Montalbetti, James G Rooney, Allison L Marciszyn, Marcelo D Carattino
Acid-sensing ion channels (ASICs) are trimeric proton-activated cation selective neuronal channels that are considered to play important roles in mechanosensation and nociception. Here we investigated the role of ASIC3, a subunit primarily expressed in sensory neurons, in bladder sensory signaling and function. We found that extracellular acidification evokes a transient increase in current, consistent with the kinetics of activation and desensitization of ASICs, in ~ 25% of the bladder sensory neurons harvested from both wild type (WT) and ASIC3 knockout (KO) mice...
March 21, 2018: American Journal of Physiology. Renal Physiology
Xuan-Rui Zhang, You-Ping Xu, Xin-Zhong Cai
Mechanisms underlying plant non-host resistance to Xanthomonas oryzae pv. oryzicola ( Xoc ), the pathogen causing rice leaf streak disease, are largely unknown. Cyclic nucleotide-gated ion channels (CNGCs) are calcium-permeable channels that are involved in various biological processes including plant resistance. In this study, functions of two tomato CNGC genes SlCNGC1 and SlCNGC14 in non-host resistance to Xoc were analyzed. Silencing of SlCNGC1 and SlCNGC14 in tomato significantly enhanced Xoc -induced hypersensitive response (HR) and non-host resistance, demonstrating that both SlCNGC1 and SlCNGC14 negatively regulate non-host resistance related HR and non-host resistance to Xoc in tomato...
2018: Frontiers in Plant Science
Monika Lakk, Felix Vazquez-Chona, Oleg Yarishkin, David Križaj
Unesterified cholesterol controls the fluidity, permeability and electrical properties of eukaryotic cell membranes. Consequently, cholesterol levels in the retina and the brain are tightly regulated whereas depletion or oversupply caused by diet or heredity contribute to neurodegenerative diseases and vision loss. Astroglia play a central role in the biosynthesis, uptake and transport of cholesterol and also drive inflammatory signaling under hypercholesterolemic conditions associated with high-fat diet (diabetes) and neurodegenerative disease...
February 2018: Neural Regeneration Research
Xiu-Xiu Zhang, Yi-Zhen Song, Fang Fang, Zhi-Yong Wu
On-site rapid monitoring of nitrite as an assessment indicator of the environment, food, and physiological systems has drawn extensive attention. Here, electrokinetic stacking (ES) was combined with colorimetric reaction on a paper-based device (PAD) to achieve colorless nitrite detection with smartphone. In this paper, nitrite was stacked on the paper fluidic channel as a narrow band by electrokinetic stacking. Then, Griess reagent was introduced to visualize the stacking band. Under optimal conditions, the sensitivity of nitrite was 160-fold increased within 5 min...
March 19, 2018: Analytical and Bioanalytical Chemistry
Michaela Lichtenegger, Oleksandra Tiapko, Barbora Svobodova, Thomas Stockner, Toma N Glasnov, Wolfgang Schreibmayer, Dieter Platzer, Gema Guedes de la Cruz, Sarah Krenn, Romana Schober, Niroj Shrestha, Rainer Schindl, Christoph Romanin, Klaus Groschner
Transient receptor potential canonical (TRPC) channels TRPC3, TRPC6 and TRPC7 are able to sense the lipid messenger diacylglycerol (DAG). The DAG-sensing and lipid-gating processes in these ion channels are still unknown. To gain insights into the lipid-sensing principle, we generated a DAG photoswitch, OptoDArG, that enabled efficient control of TRPC3 by light. A structure-guided mutagenesis screen of the TRPC3 pore domain unveiled a single glycine residue behind the selectivity filter (G652) that is exposed to lipid through a subunit-joining fenestration...
March 19, 2018: Nature Chemical Biology
Albert Ardevol, Gerhard Hummer
Channelrhodopsin-2 (ChR2) is a light-sensitive ion channel widely used in optogenetics. Photoactivation triggers a trans -to- cis isomerization of a covalently bound retinal. Ensuing conformational changes open a cation-selective channel. We explore the structural dynamics in the early photocycle leading to channel opening by classical (MM) and quantum mechanical (QM) molecular simulations. With QM/MM simulations, we generated a protein-adapted force field for the retinal chromophore, which we validated against absorption spectra...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Iva Hafner-Bratkovič, Pablo Pelegrín
The NLRP3 inflammasome is a multiprotein platform for the activation of caspase-1, which in turn drives inflammation through the activation of proinflammatory cytokines, such as IL-1β. In contrast to the majority of pattern recognition receptors, NLRP3 inflammasome can be triggered by a plethora of pathogen-derived or endogenous activators, which perturb intracellular ion homeostasis. Here, we discuss how the complex interplay of ion fluxes contributes to canonical, non-canonical, and alternative NLRP3 activation pathways that induce IL-1β secretion from immune cells...
March 16, 2018: Current Opinion in Immunology
Shunjie Ye, Rong Yang, Qiuju Xiong, Youhua Yang, Lianying Zhou, Yeli Gong, Changlei Li, Zhenhan Ding, Guohai Ye, Zhe Xiong
Acute stress has been shown to enhance learning and memory ability, predominantly through the action of corticosteroid stress hormones. However, the valuable targets for promoting learning and memory induced by acute stress and the underlying molecular mechanisms remain unclear. Acid-sensing ion channels (ASICs) play an important role in central neuronal systems and involves in depression, synaptic plasticity and learning and memory. In the current study, we used a combination of electrophysiological and behavioral approaches in an effort to explore the effects of acute stress on ASICs...
March 16, 2018: Biochemical and Biophysical Research Communications
Daiju Yamazaki, Takashi Kitaguchi, Masakazu Ishimura, Tomohiko Taniguchi, Atsuhiro Yamanishi, Daisuke Saji, Etsushi Takahashi, Masao Oguchi, Yuta Moriyama, Sanae Maeda, Kaori Miyamoto, Kaoru Morimura, Hiroki Ohnaka, Hiroyuki Tashibu, Yuko Sekino, Norimasa Miyamoto, Yasunari Kanda
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are expected to become a useful tool for proarrhythmia risk prediction in the non-clinical drug development phase. Several features including electrophysiological properties, ion channel expression profile and drug responses were investigated using commercially available hiPSC-CMs, such as iCell-CMs and Cor.4U-CMs. Although drug-induced arrhythmia has been extensively examined by microelectrode array (MEA) assays in iCell-CMs, it has not been fully understood an availability of Cor...
March 3, 2018: Journal of Pharmacological Sciences
Govindaraj Anumanthan, Suneel Gupta, Michael K Fink, Nathan P Hesemann, Douglas K Bowles, Lindsey M McDaniel, Maaz Muhammad, Rajiv R Mohan
Vision impairment from corneal fibrosis is a common consequence of irregular corneal wound healing after injury. Intermediate-conductance calmodulin/calcium-activated K+ channels 3.1 (KCa3.1) play an important role in cell cycle progression and cellular proliferation. Proliferation and differentiation of corneal fibroblasts to myofibroblasts can lead to corneal fibrosis after injury. KCa3.1 has been shown in many non-ocular tissues to promote fibrosis, but its role in corneal fibrosis is still unknown. In this study, we characterized the expression KCa3...
2018: PloS One
Chun-Hsiang Tan, Peter A McNaughton
The abilities to detect warmth and heat are critical for the survival of all animals, both in order to be able to identify suitable thermal environments for the many different activities essential for life and to avoid damage caused by extremes of temperature. Several ion channels belonging to the TRP family are activated by non-noxious warmth or by heat and are therefore plausible candidates for thermal detectors, but identifying those that actually regulate warmth and heat detection in intact animals has proven problematic...
March 19, 2018: Pflügers Archiv: European Journal of Physiology
Wen Chen, Jyoti Dev, Julija Mezhyrova, Liqiang Pan, Alessandro Piai, James J Chou
The p7 protein of the hepatitis C virus (HCV) can oligomerize in membrane to form cation channels. Previous studies showed that the channel assembly in detergent micelles adopts a unique flower-shaped oligomer, but the unusual architecture also presented problems for understanding how this viroporin resides in the membrane. Moreover, the oligomeric state of p7 remains controversial, as both hexamer and heptamer have been proposed. Here we address the above issues using p7 reconstituted in bicelles that mimic a lipid bilayer...
February 27, 2018: Structure
Miyuki Kuno
A proton is a ubiquitous signaling ion. Many transmembrane H+ transport pathways either maintain pH homeostasis or generate acidic compartments. The osteoclast is a bone-resorbing cell, which degrades bone tissues by secreting protons and lysosomal enzymes into the resorption pit. The plasma membrane facing bone tissue (ruffled border), generated partly by fusion of lysosomes, may mimic H+ flux mechanisms regulating acidic vesicles. We identified three electrogenic H+ -fluxes in osteoclast plasma membranes-a vacuolar H+ -ATPase (V-ATPase), a voltage-gated proton channel (Hv channel) and an acid-inducible H+ -leak-whose electrophysiological profiles and regulation mechanisms differed...
March 17, 2018: Pflügers Archiv: European Journal of Physiology
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