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https://read.qxmd.com/read/30931713/overlap-of-periodic-paralysis-and-paramyotonia-congenita-caused-by-scn4a-gene-mutations
#1
Shan Huang, Wei Zhang, Xueli Chang, Junhong Guo
Objective To verify the diagnosis of channelopathies in two families and explore the mechanism of the overlap between periodic paralysis (PP) and paramyotonia congenita (PMC). Methods We have studied two cases with overlapping symptoms of episodic weakness and stiffness in our clinical center using a series of assessment including detailed medical history, careful physical examination, laboratory analyses, muscle biopsy, electrophysiological evaluation, and genetic analysis. Results The first proband and part of his family with the overlap of PMC and hyperkalemic periodic paralysis (HyperPP) has been identified as c...
April 1, 2019: Channels
https://read.qxmd.com/read/30983497/cachd1-a-new-activity-modifying-protein-for-voltage-gated-calcium-channels
#2
Gary J Stephens, Graeme S Cottrell
No abstract text is available yet for this article.
December 2019: Channels
https://read.qxmd.com/read/30885080/fluorescence-microscopy-of-piezo1-in-droplet-hydrogel-bilayers
#3
Oskar B Jaggers, Pietro Ridone, Boris Martinac, Matthew A B Baker
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 imaging of labelled protein...
December 2019: Channels
https://read.qxmd.com/read/30712450/kv2-channels-create-endoplasmic-reticulum-plasma-membrane-junctions-a-brief-history-of-kv2-channel-subcellular-localization
#4
Ben Johnson, Ashley N Leek, Michael M Tamkun
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...
December 2019: Channels
https://read.qxmd.com/read/30704344/regional-differences-in-the-expression-of-tetrodotoxin-sensitive-inward-ca-2-and-outward-cs-k-currents-in-mouse-and-human-ventricles
#5
Wei Wang, Rebecca L Mellor, Jeanne M Nerbonne, C William Balke
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 LV endocardium and epicardium...
December 2019: Channels
https://read.qxmd.com/read/30672394/inhibition-of-multiple-voltage-gated-calcium-channels-may-contribute-to-spinally-mediated-analgesia-by-epipregnanolone-in-a-rat-model-of-surgical-paw-incision
#6
Sonja Lj Joksimovic, Rebecca R Donald, Ji-Yong Park, Slobodan M Todorovic
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 vivo, after local intraplantar application into the foot pads of heathy rats and mice...
December 2019: Channels
https://read.qxmd.com/read/30672373/lifting-the-veils-on-tmem16e-function
#7
Anna Boccaccio, Eleonora Di Zanni, Antonella Gradogna, Joachim Scholz-Starke
No abstract text is available yet for this article.
December 2019: Channels
https://read.qxmd.com/read/30661462/arachidonic-acid-hyperpolarizes-mesenchymal-stromal-cells-from-the-human-adipose-tissue-by-stimulating-trek1-k-channels
#8
Michail V Tarasov, Polina D Kotova, Marina F Bystrova, Natalia V Kabanova, Veronika Yu Sysoeva, Stanislav S Kolesnikov
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+ channels, K2P channels from the TREK subfamily appeared to be an appropriate target...
December 2019: Channels
https://read.qxmd.com/read/30638110/correcting-the-r165k-substitution-in-the-first-voltage-sensor-of-ca-v-1-1-right-shifts-the-voltage-dependence-of-skeletal-muscle-calcium-channel-activation
#9
Yousra El Ghaleb, Marta Campiglio, Bernhard E Flucher
The voltage-gated calcium channel CaV 1.1a primarily functions as voltage-sensor in skeletal muscle excitation-contraction (EC) coupling. In embryonic muscle the splice variant CaV 1.1e, which lacks exon 29, additionally function as a genuine L-type calcium channel. Because previous work in most laboratories used a CaV 1.1 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 currents in dysgenic myotubes...
January 14, 2019: Channels
https://read.qxmd.com/read/30477399/rectification-ratio-based-determination-of-disulfide-bonds-of-%C3%AE-2-extracellular-loop-of-bk-channel
#10
Xiying Guo, Haowen Liu, Zhigang Huang, Yanting Wang, Yan Zhang, Lu-Yang Wang, Chunyang Cao, Sheng Wang, Jiuping Ding
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 properties. Its extracellular loop contains eight cysteine residues, which can pair to form a high-order structure, underlying the stability of the extracellular loop of β2 subunits and the functional effects on BK channels...
November 26, 2018: Channels
https://read.qxmd.com/read/30424709/-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
#11
Jaime S Horton, Takuya Shiraishi, Naghum Alfulaij, Andrea L Small-Howard, Helen C Turner, Tatsuki Kurokawa, Yasuo Mori, Alexander J Stokes
Background Activation of the atrial natriuretic signaling pathway is intrinsic to the pathological responses associated with a range of cardiovascular diseases that stress the heart, especially those involved in sustained cardiac pressure overload which induces hypertrophy and the pathological remodeling that frequently leads to heart failure. We identify transient receptor potential cation channel, subfamily V, member 1, as a regulated component, and therapeutic target of this signaling system. Methods We undertook biochemical, calcium imaging and electrophysiological experiments to analyze interactions and regulation of TRPV1...
November 13, 2018: Channels
https://read.qxmd.com/read/30403912/role-of-individual-s4-segments-in-gating-of-ca-v-3-1-t-type-calcium-channel-by-voltage
#12
Bohumila Jurkovicova Tarabova, Katarina Mackova, Lucia Moravcikova, Maria Karmazinova, Lubica Lacinova
Contributions of voltage sensing S4 segments in domains I - IV of CaV 3.1 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 mutation in domain I and by double mutations in domains I + II and I + IV...
November 7, 2018: Channels
https://read.qxmd.com/read/30362397/effects-of-acidosis-on-neuronal-voltage-gated-sodium-channels-nav1-1-and-nav1-3
#13
Mohammad-Reza Ghovanloo, Colin H Peters, Peter C Ruben
Voltage-gated sodium channels are key contributors to membrane excitability. These channels are expressed in a tissue-specific manner. Mutations and modulation of these channels underlie various physiological and pathophysiological manifestations. The effects of changes in extracellular pH on channel gating have been studied on several sodium channel subtypes. Among these, Nav1.5 is the most pH-sensitive channel, with Nav1.2 and Nav1.4 being mostly pH-resistant channels. However, pH effects have not been characterized on other sodium channel subtypes...
October 26, 2018: Channels
https://read.qxmd.com/read/30134757/bibliometric-analysis-of-recent-sodium-channel-research
#14
Dongyi Zhao, Jianing Li, Corey Seehus, Xuan Huang, Meimi Zhao, Shiqi Zhang, Wuyang Wang, Hong-Long Ji, Feng Guo
No abstract text is available yet for this article.
August 23, 2018: Channels
https://read.qxmd.com/read/30465465/gating-defects-of-disease-causing-de-novo-mutations-in-ca-v-1-3-ca-2-channels
#15
Alexandra Pinggera, Giulia Negro, Petronel Tuluc, Morris J Brown, Andreas Lieb, Jörg Striessnig
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 Cav 1.3 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 their pathogenic potential is difficult to predict in silico, making functional studies indispensable to assess their contribution to disease risk...
2018: Channels
https://read.qxmd.com/read/30301404/potassium-channels-in-the-sinoatrial-node-and-their-role-in-heart-rate-control
#16
Qadeer Aziz, Yiwen Li, Andrew Tinker
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.
2018: Channels
https://read.qxmd.com/read/30264650/role-of-the-alternative-splice-variant-of-ncc-in-blood-pressure-control
#17
Hila Wardak, Omar A Z Tutakhel, Jenny Van Der Wijst
The renal thiazide-sensitive sodium-chloride cotransporter (NCC), located in the distal convoluted tubule (DCT) of the kidney, plays an important role in blood pressure regulation by fine-tuning sodium excretion. The human SLC12A3 gene, encoding NCC, gives rise to three isoforms, of which only the third isoform (NCC3 ) has been extensively investigated so far. However, recent studies unraveled the importance of the isoforms 1 and 2, collectively referred to as NCC splice variant (NCCSV ), in several (patho)physiological conditions...
2018: Channels
https://read.qxmd.com/read/30165790/in-vitro-and-in-vivo-phosphorylation-of-the-ca-v-2-3-voltage-gated-r-type-calcium-channel
#18
T Schneider, S Alpdogan, J Hescheler, F Neumaier
During the recording of whole cell currents from stably transfected HEK-293 cells, the decline of currents carried by the recombinant human Cav2.3+β3 channel subunits is related to adenosine triphosphate (ATP) depletion after rupture of the cells. It reduces the number of functional channels and leads to a progressive shift of voltage-dependent gating to more negative potentials (Neumaier F., et al., 2018). Both effects can be counteracted by hydrolysable ATP, whose protective action is almost completely prevented by inhibition of serine/threonine but not tyrosine or lipid kinases...
2018: Channels
https://read.qxmd.com/read/30165782/the-role-of-the-unfolded-protein-response-in-arrhythmias
#19
Man Liu, Samuel C Dudley
Human heart failure is characterized by arrhythmogenic electrical remodeling consisting mostly of ion channel downregulations. Reversing these downregulations is a logical approach to antiarrhythmic therapy, but understanding the pathophysiological mechanisms of the reduced currents is crucial for finding the proper treatments. The unfolded protein response (UPR) is activated by endoplasmic reticulum (ER) stress and has been found to play pivotal roles in different diseases including neurodegenerative diseases, diabetes mellitus, and heart disease...
2018: Channels
https://read.qxmd.com/read/30152709/cystic-fibrosis-transmembrane-conductance-regulator-cftr-making-an-ion-channel-out-of-an-active-transporter-structure
#20
Paul Linsdell
Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is a member of the ATP-binding cassette (ABC) family of membrane transport proteins, most members of which function as ATP-dependent pumps. CFTR is unique among human ABC proteins in functioning not as a pump, but as an ion channel. Recent structural data has indicated that CFTR shares broadly similar overall architecture and ATP-dependent conformational changes as other ABC proteins. Functional investigations suggest that CFTR has a unique open portal connecting the cytoplasm to the transmembrane channel pore, that allows for a continuous pathway for Cl- ions to cross the membrane in one conformation...
2018: Channels
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