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Journal of General Physiology

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https://www.readbyqxmd.com/read/29776992/cardiomyopathy-mutation-f88l-in-troponin-t-abolishes-length-dependency-of-myofilament-ca-2-sensitivity
#1
Sherif M Reda, Murali Chandra
Recent clinical studies have revealed a new hypertrophic cardiomyopathy-associated mutation (F87L) in the central region of human cardiac troponin T (TnT). However, despite its implication in several incidences of sudden cardiac death in young and old adults, whether F87L is associated with cardiac contractile dysfunction is unknown. Because the central region of TnT is important for modulating the muscle length-mediated recruitment of new force-bearing cross-bridges (XBs), we hypothesize that the F87L mutation causes molecular changes that are linked to the length-dependent activation of cardiac myofilaments...
May 18, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29769228/correction-otopetrin-1-a-sour-tasting-proton-channel
#2
I Scott Ramsey, John A DeSimone
No abstract text is available yet for this article.
May 16, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29769227/influences-cold-spring-harbor-summer-courses-and-drosophila-melanogaster-neurogenetics
#3
Lily Yeh Jan, Yuh Nung Jan
No abstract text is available yet for this article.
May 16, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29769226/membrane-mediated-interaction-drives-mitochondrial-atpase-assembly-and-cristae-formation
#4
Qiang Cui
No abstract text is available yet for this article.
May 16, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29764925/the-acid-test-for-ph-dependent-gating-in-cloned-h-v-1-channels
#5
León D Islas
No abstract text is available yet for this article.
May 15, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29752414/ligand-binding-and-activation-properties-of-the-purified-bacterial-cyclic-nucleotide-gated-channel-sthk
#6
Philipp A M Schmidpeter, Xiaolong Gao, Vikrant Uphadyay, Jan Rheinberger, Crina M Nimigean
Cyclic nucleotide-modulated ion channels play several essential physiological roles. They are involved in signal transduction in photoreceptors and olfactory sensory neurons as well as pacemaking activity in the heart and brain. Investigations of the molecular mechanism of their actions, including structural and electrophysiological characterization, are restricted by the availability of stable, purified protein obtained from accessible systems. Here, we establish that SthK, a cyclic nucleotide-gated (CNG) channel from Spirochaeta thermophila , is an excellent model for investigating the gating of eukaryotic CNG channels at the molecular level...
May 11, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29743301/exotic-properties-of-a-voltage-gated-proton-channel-from-the-snail-helisoma-trivolvis
#7
Sarah Thomas, Vladimir V Cherny, Deri Morgan, Liana R Artinian, Vincent Rehder, Susan M E Smith, Thomas E DeCoursey
Voltage-gated proton channels, HV 1, were first reported in Helix aspersa snail neurons. These H+ channels open very rapidly, two to three orders of magnitude faster than mammalian HV 1. Here we identify an HV 1 gene in the snail Helisoma trivolvis and verify protein level expression by Western blotting of H. trivolvis brain lysate. Expressed in mammalian cells, HtHV 1 currents in most respects resemble those described in other snails, including rapid activation, 476 times faster than hHV 1 (human) at pHo 7, between 50 and 90 mV...
May 9, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29743300/histidine-168-is-crucial-for-%C3%AE-ph-dependent-gating-of-the-human-voltage-gated-proton-channel-hh-v-1
#8
Vladimir V Cherny, Deri Morgan, Sarah Thomas, Susan M E Smith, Thomas E DeCoursey
We recently identified a voltage-gated proton channel gene in the snail Helisoma trivolvis , HtHV 1, and determined its electrophysiological properties. Consistent with early studies of proton currents in snail neurons, HtHV 1 opens rapidly, but it unexpectedly exhibits uniquely defective sensitivity to intracellular pH (pHi ). The H+ conductance ( g H )- V relationship in the voltage-gated proton channel (HV 1) from other species shifts 40 mV when either pHi or pHo (extracellular pH) is changed by 1 unit. This property, called ΔpH-dependent gating, is crucial to the functions of HV 1 in many species and in numerous human tissues...
May 9, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29743299/the-akap-cypher-zasp-contributes-to-%C3%AE-adrenergic-pka-stimulation-of-cardiac-ca-v-1-2-calcium-channels
#9
Haijie Yu, Can Yuan, Ruth E Westenbroek, William A Catterall
Stimulation of the L-type Ca2+ current conducted by CaV 1.2 channels in cardiac myocytes by the β-adrenergic/protein kinase A (PKA) signaling pathway requires anchoring of PKA to the CaV 1.2 channel by an A-kinase anchoring protein (AKAP). However, the AKAP(s) responsible for regulation in vivo remain unknown. Here, we test the role of the AKAP Cypher/Zasp in β-adrenergic regulation of CaV 1.2 channels using physiological studies of cardiac ventricular myocytes from young-adult mice lacking the long form of Cypher/Zasp (LCyphKO mice)...
May 9, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29743298/coupling-between-an-electrostatic-network-and-the-zn-2-binding-site-modulates-hv1-activation
#10
Victor De La Rosa, Ashley L Bennett, Ian Scott Ramsey
The voltage sensor (VS) domain in Hv1 proton channels mediates a voltage-dependent and H+ -selective "aqueous" conductance (GAQ ) that is potently modulated by extracellular Zn2+ Although two conserved His residues are required for Zn2+ effects on GAQ gating, the atomic structure of the Zn2+ coordination site and mechanism by which extracellular Zn2+ stabilizes a closed-state conformation remain unknown. Here we use His mutagenesis to identify residues that increase Zn2+ potency and are therefore likely to participate in first solvation shell interactions with Zn2+ Experimental Zn2+ -mapping data were then used to constrain the structure of a new resting-state Hv1 model (Hv1 F)...
May 9, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29703838/structural-insights-into-the-molecular-mechanism-of-mouse-trpa1-activation-and-inhibition
#11
Amrita Samanta, Janna Kiselar, Ruth A Pumroy, Seungil Han, Vera Y Moiseenkova-Bell
Pain, though serving the beneficial function of provoking a response to dangerous situations, is an unpleasant sensory and emotional experience. Transient receptor potential ankyrin 1 (TRPA1) is a member of the transient receptor potential (TRP) cation channel family and is localized in "nociceptors," where it plays a key role in the transduction of chemical, inflammatory, and neuropathic pain. TRPA1 is a Ca2+ -permeable, nonselective cation channel that is activated by a large variety of structurally unrelated electrophilic and nonelectrophilic chemical compounds...
April 27, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29695412/dimerization-of-the-voltage-sensing-phosphatase-controls-its-voltage-sensing-and-catalytic-activity
#12
Vamseedhar Rayaprolu, Perrine Royal, Karen Stengel, Guillaume Sandoz, Susy C Kohout
Multimerization is a key characteristic of most voltage-sensing proteins. The main exception was thought to be the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP). In this study, we show that multimerization is also critical for Ci-VSP function. Using coimmunoprecipitation and single-molecule pull-down, we find that Ci-VSP stoichiometry is flexible. It exists as both monomers and dimers, with dimers favored at higher concentrations. We show strong dimerization via the voltage-sensing domain (VSD) and weak dimerization via the phosphatase domain...
April 25, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29695411/influences-childhood-boyhood-and-youth
#13
Christopher Miller
No abstract text is available yet for this article.
April 25, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29685928/cryo-electron-microscopy-structures-and-progress-toward-a-dynamic-understanding-of-k-atp-channels
#14
REVIEW
Michael C Puljung
Adenosine triphosphate (ATP)-sensitive K+ (KATP ) channels are molecular sensors of cell metabolism. These hetero-octameric channels, comprising four inward rectifier K+ channel subunits (Kir6.1 or Kir6.2) and four sulfonylurea receptor (SUR1 or SUR2A/B) subunits, detect metabolic changes via three classes of intracellular adenine nucleotide (ATP/ADP) binding site. One site, located on the Kir subunit, causes inhibition of the channel when ATP or ADP is bound. The other two sites, located on the SUR subunit, excite the channel when bound to Mg nucleotides...
April 23, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29685927/deafness-associated-mutation-opens-the-gate-to-understanding
#15
Caitlin Sedwick
New JGP study uncovers a connection between Connexin 26 fast and slow gates.
April 23, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29680816/full-and-partial-agonists-evoke-distinct-structural-changes-in-opening-the-muscle-acetylcholine-receptor-channel
#16
Nuriya Mukhtasimova, Steven M Sine
The muscle acetylcholine (ACh) receptor transduces a chemical into an electrical signal, but the efficiency of transduction, or efficacy, depends on the particular agonist. It is often presumed that full and partial agonists elicit the same structural changes after occupancy of their binding sites but with differing speed and efficiency. In this study, we tested the alternative hypothesis that full and partial agonists elicit distinct structural changes. To probe structural changes, we substituted cysteines for pairs of residues that are juxtaposed in the three-dimensional structure and recorded agonist-elicited single-channel currents before and after the addition of an oxidizing reagent...
April 21, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29666153/the-ins-and-outs-of-vesicular-monoamine-transporters
#17
REVIEW
Dana Yaffe, Lucy R Forrest, Shimon Schuldiner
The H+ -coupled vesicular monoamine transporter (VMAT) is a transporter essential for life. VMAT mediates packaging of the monoamines serotonin, dopamine, norepinephrine, and histamine from the neuronal cytoplasm into presynaptic vesicles, which is a key step in the regulated release of neurotransmitters. However, a detailed understanding of the mechanism of VMAT function has been limited by the lack of availability of high-resolution structural data. In recent years, a series of studies guided by homology models has revealed significant insights into VMAT function, identifying residues that contribute to the binding site and to specific steps in the transport cycle...
April 17, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29643173/-mitochondrial-atp-synthase-dimers-spontaneously-associate-due-to-a-long-range-membrane-induced-force
#18
Claudio Anselmi, Karen M Davies, José D Faraldo-Gómez
Adenosine triphosphate (ATP) synthases populate the inner membranes of mitochondria, where they produce the majority of the ATP required by the cell. From yeast to vertebrates, cryoelectron tomograms of these membranes have consistently revealed a very precise organization of these enzymes. Rather than being scattered throughout the membrane, the ATP synthases form dimers, and these dimers are organized into rows that extend for hundreds of nanometers. The rows are only observed in the membrane invaginations known as cristae, specifically along their sharply curved edges...
April 11, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29643172/the-syndromic-deafness-mutation-g12r-impairs-fast-and-slow-gating-in-cx26-hemichannels
#19
Isaac E García, Felipe Villanelo, Gustavo F Contreras, Amaury Pupo, Bernardo I Pinto, Jorge E Contreras, Tomás Pérez-Acle, Osvaldo Alvarez, Ramon Latorre, Agustín D Martínez, Carlos González
Mutations in connexin 26 (Cx26) hemichannels can lead to syndromic deafness that affects the cochlea and skin. These mutations lead to gain-of-function hemichannel phenotypes by unknown molecular mechanisms. In this study, we investigate the biophysical properties of the syndromic mutant Cx26G12R (G12R). Unlike wild-type Cx26, G12R macroscopic hemichannel currents do not saturate upon depolarization, and deactivation is faster during hyperpolarization, suggesting that these channels have impaired fast and slow gating...
April 11, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29626041/atom-by-atom-tuning-of-the-electrostatic-potassium-channel-modulator-dehydroabietic-acid
#20
Malin Silverå Ejneby, Xiongyu Wu, Nina E Ottosson, E Peter Münger, Ingemar Lundström, Peter Konradsson, Fredrik Elinder
Dehydroabietic acid (DHAA) is a naturally occurring component of pine resin that was recently shown to open voltage-gated potassium (KV ) channels. The hydrophobic part of DHAA anchors the compound near the channel's positively charged voltage sensor in a pocket between the channel and the lipid membrane. The negatively charged carboxyl group exerts an electrostatic effect on the channel's voltage sensor, leading to the channel opening. In this study, we show that the channel-opening effect increases as the length of the carboxyl-group stalk is extended until a critical length of three atoms is reached...
April 6, 2018: Journal of General Physiology
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