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https://www.readbyqxmd.com/read/28316260/animal-physiology-and-genetic-aspects-of-ryegrass-staggers-in-grazing-sheep
#1
C A Morris, T T Wheeler, H V Henderson, N R Towers, S H Phua
Ryegrass staggers (RGS) is a metabolic disease of herbivores, caused by the ingestion of perennial ryegrass (Lolium perenne L.) containing a fungal endophyte (Neotyphodium lolii) which produces a tremorgenic toxin, lolitrem B. RGS has a major economic impact for agriculture in New Zealand as well as internationally. Management of RGS in grazing sheep can be problematic, and there is an incomplete knowledge of the interaction between the toxin and the grazing animal. This review is focused on recent advances in understanding the molecular physiology of RGS in the affected animal as well as the influence of animal genetics on the degree of susceptibility to RGS...
March 19, 2017: New Zealand Veterinary Journal
https://www.readbyqxmd.com/read/28294531/tyrphostin-ag556-increases-the-activity-of-large-conductance-ca-2-activated-k-channels-by-inhibiting-epidermal-growth-factor-receptor-tyrosine-kinase
#2
Yan Wang, Hai-Ying Sun, Ying-Guang Liu, Zheng Song, Gang She, Guo-Sheng Xiao, Yan Wang, Gui-Rong Li, Xiu-Ling Deng
The present study was designed to investigate whether large conductance Ca(2+) -activated K(+) (BK) channels were regulated by epidermal growth factor (EGF) receptor (EGFR) tyrosine kinase. BK current and channel tyrosine phosphorylation level were measured in BK-HEK 293 cells expressing both functional α-subunits and the auxiliary β1-subunits using electrophysiology, immunoprecipitation and Western blotting approaches, respectively, and the function of rat cerebral basilar arteries was determined with a wire myography system...
March 14, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28294142/inosine-attenuates-spontaneous-activity-in-the-rat-neurogenic-bladder-through-an-a2b-pathway
#3
Claire Doyle, Vivian Cristofaro, Bryan S Sack, Stefan N Lukianov, Mattias Schäfer, Yeun Goo Chung, Maryrose P Sullivan, Rosalyn M Adam
Neurogenic detrusor overactivity (NDO) is among the most challenging complications of spinal cord injury (SCI). A recent report by us demonstrated an improvement in NDO in SCI rats following chronic systemic treatment with the purine nucleoside inosine. The objective of this study was to investigate the mechanism of action of inosine underlying improvement of NDO. Male Sprague-Dawley rats underwent complete spinal cord transection at T8. Inosine (1 mM) delivered intravesically to SCI rats during conscious cystometry significantly decreased the frequency of spontaneous non-voiding contractions...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28289383/the-citrus-flavanone-naringenin-produces-cardioprotective-effects-in-hearts-from-1-year-old-rat-through-activation-of-mitobk-channels
#4
Lara Testai, Eleonora Da Pozzo, Ilaria Piano, Luisa Pistelli, Claudia Gargini, Maria Cristina Breschi, Alessandra Braca, Claudia Martini, Alma Martelli, Vincenzo Calderone
Background and Purpose: Incidence of cardiovascular disorders increases with age, because of a dramatic fall of endogenous self-defense mechanisms and increased vulnerability of myocardium. Conversely, the effectiveness of many cardioprotective drugs is blunted in hearts of 1 year old rat. The Citrus flavanone naringenin (NAR) was reported to promote cardioprotective effects against ischemia/reperfusion (I/R) injury, through the activation of mitochondrial large conductance calcium-activated potassium channel (mitoBK)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28289184/renal-tubular-ubiquitin-protein-ligase-nedd4-2-is-required-for-renal-adaptation-during-long-term-potassium-depletion
#5
Lama Al-Qusairi, Denis Basquin, Ankita Roy, Renuga Devi Rajaram, Marc P Maillard, Arohan R Subramanya, Olivier Staub
Adaptation of the organism to potassium (K(+)) deficiency requires precise coordination among organs involved in K(+) homeostasis, including muscle, liver, and kidney. How the latter performs functional and molecular changes to ensure K(+) retention is not well understood. Here, we investigated the role of ubiquitin-protein ligase NEDD4-2, which negatively regulates the epithelial sodium channel (ENaC), Na(+)/Cl(-) cotransporter (NCC), and with no-lysine-kinase 1 (WNK1). After dietary K(+) restriction for 2 weeks, compared with control littermates, inducible renal tubular NEDD4-2 knockout (Nedd4L(Pax8/LC1) ) mice exhibited severe hypokalemia and urinary K(+) wasting...
March 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28283888/kinin-receptors-sensitize-trpv4-channel-and-induce-mechanical-hyperalgesia-relevance-to-paclitaxel-induced-peripheral-neuropathy-in-mice
#6
Robson Costa, Maíra A Bicca, Marianne N Manjavachi, Gabriela C Segat, Fabiana Chaves Dias, Elizabeth S Fernandes, João B Calixto
Kinin B1 (B1R) and B2 receptors (B2R) and the transient receptor potential vanilloid 4 (TRPV4) channel are known to play a critical role in the peripheral neuropathy induced by paclitaxel (PTX) in rodents. However, the downstream pathways activated by kinin receptors as well as the sensitizers of the TRPV4 channel involved in this process remain unknown. Herein, we investigated whether kinins sensitize TRPV4 channels in order to maintain PTX-induced peripheral neuropathy in mice. The mechanical hyperalgesia induced by bradykinin (BK, a B2R agonist) or des-Arg(9)-BK (DABK, a B1R agonist) was inhibited by the selective TRPV4 antagonist HC-067047...
March 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28274924/dynamic-coupling-between-trpv4-and-ca-activated-sk1-3-and-ik1-k-channels-plays-a-critical-role-in-regulating-the-k-secretory-bk-channel-in-collecting-duct-cells
#7
Yue Li, Hongxiang Hu, Jin-Bin Tian, Michael X Zhu, Roger G O'Neil
The large conductance Ca2+-activated K+ channel, BK (KCNMA1), is expressed along the connecting tubule (CNT) and cortical collecting duct (CCD) where it underlies flow- and Ca2+-dependent K+ secretion. Its activity is partially under the control of the mechanosensitive TRPV4 Ca2+-permeable channel. Recently we identified three small/intermediate conductance Ca2+-activated K+ channels, SK1 (KCNN1) and SK3 (KCNN3), and IK1 (KCNN4), with notably high Ca2+-binding affinities, that are expressed in CNT/CCD and may be regulated by TRPV4-mediated Ca2+ influx...
March 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28264196/molecular-basis-of-ancestral-vertebrate-electroreception
#8
Nicholas W Bellono, Duncan B Leitch, David Julius
Elasmobranch fishes, including sharks, rays, and skates, use specialized electrosensory organs called ampullae of Lorenzini to detect extremely small changes in environmental electric fields. Electrosensory cells within these ampullae can discriminate and respond to minute changes in environmental voltage gradients through an unknown mechanism. Here we show that the voltage-gated calcium channel CaV1.3 and the big conductance calcium-activated potassium (BK) channel are preferentially expressed by electrosensory cells in little skate (Leucoraja erinacea) and functionally couple to mediate electrosensory cell membrane voltage oscillations, which are important for the detection of specific, weak electrical signals...
March 16, 2017: Nature
https://www.readbyqxmd.com/read/28246116/understanding-the-conformational-motions-of-rck-gating-rings
#9
REVIEW
Teresa Giraldez, Brad S Rothberg
Regulator of conduction of K(+) (RCK) domains are ubiquitous regulators of channel and transporter activity in prokaryotes and eukaryotes. In humans, RCK domains form an integral component of large-conductance calcium-activated K channels (BK channels), key modulators of nerve, muscle, and endocrine cell function. In this review, we explore how the study of RCK domains in bacterial and human channels has contributed to our understanding of the structural basis of channel function. This knowledge will be critical in identifying mechanisms that underlie BK channelopathies that lead to epilepsy and other diseases, as well as regions of the channel that might be successfully targeted to treat such diseases...
February 28, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28242822/survival-and-growth-of-c57bl-6j-mice-lacking-the-bk-channel-kcnma1-lower-adult-body-weight-occurs-together-with-higher-body-fat
#10
Susan T Halm, Michael A Bottomley, Mohammed M Almutairi, Maurico Di Fulvio, Dan R Halm
Big conductance potassium (BK) channels contribute to K(+) flow and electrical behavior in many cell types. Mice made null for the gene (Kcnma1) producing the BK channel (BK(KO)) exhibit numerous deficits in physiological functions. Breeding mice lacking a single allele of Kcnma1 (C57BL/6J background) had litter sizes of approximately eight pups. For the period of maternal care (P0-P21), pup deaths peaked at P1 with a second less severe interval of death peaking near P13. Early deaths were twice as likely during a 20-month period of building construction compared with the quiescent period after cessation of construction...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28237360/involvement-of-wnk1-mediated-potassium-channels-in-the-sexual-dimorphism-of-blood-pressure
#11
Guofeng Yu, Mengting Cheng, Wei Wang, Rong Zhao, Zhen Liu
Potassium homeostasis plays an essential role in the control of blood pressure. It is unknown, however, whether potassium balance is involved in the gender-associated blood pressure differences. We therefore investigated the possible mechanism of sexual dimorphism in blood pressure regulation by measuring the blood pressure, plasma potassium, renal actions of potassium channels and upstream regulator in male and female mice. Here we found that female mice exhibited lower blood pressure and higher plasma K(+) level as compared to male littermates...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28202492/gating-ring-strengthens-marriage-of-bk-channel-voltage-sensing-to-pore-opening
#12
Caitlin Sedwick
A new JGP study shows that the gating ring helps the voltage-sensing domain open the BK channel's pore.
March 6, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28196879/deletion-of-cytosolic-gating-ring-decreases-gate-and-voltage-sensor-coupling-in-bk-channels
#13
Guohui Zhang, Yanyan Geng, Yakang Jin, Jingyi Shi, Kelli McFarland, Karl L Magleby, Lawrence Salkoff, Jianmin Cui
Large conductance Ca(2+)-activated K(+) channels (BK channels) gate open in response to both membrane voltage and intracellular Ca(2+) The channel is formed by a central pore-gate domain (PGD), which spans the membrane, plus transmembrane voltage sensors and a cytoplasmic gating ring that acts as a Ca(2+) sensor. How these voltage and Ca(2+) sensors influence the common activation gate, and interact with each other, is unclear. A previous study showed that a BK channel core lacking the entire cytoplasmic gating ring (Core-MT) was devoid of Ca(2+) activation but retained voltage sensitivity (Budelli et al...
March 6, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28195225/a-novel-bk-channel-targeted-peptide-suppresses-sound-evoked-activity-in-the-mouse-inferior-colliculus
#14
L L Scott, E J Brecht, A Philpo, S Iyer, N S Wu, S J Mihic, R W Aldrich, J Pierce, J P Walton
Large conductance calcium-activated (BK) channels are broadly expressed in neurons and muscle where they modulate cellular activity. Decades of research support an interest in pharmaceutical applications for modulating BK channel function. Here we report a novel BK channel-targeted peptide with functional activity in vitro and in vivo. This 9-amino acid peptide, LS3, has a unique action, suppressing channel gating rather than blocking the pore of heterologously expressed human BK channels. With an IC50 in the high picomolar range, the apparent affinity is higher than known high affinity BK channel toxins...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28192090/optogenetic-control-of-ca-2-and-voltage-dependent-large-conductance-bk-potassium-channels
#15
Thomas Mager, Phillip G Wood, Ernst Bamberg
Ca(2+) concentration jumps for the activation of Ca(2+)-dependent ion channels or transporters can be obtained either by fast solution exchange or by the use of caged Ca(2+). Here, we report on an alternate optogenetic method for the activation of Ca(2+) and voltage-dependent large conductance (BK) potassium channels. This was achieved through the use of the light-gated channelrhodopsin 2 variant, CatCh(Calcium translocating Channelrhodopsin) with enhanced Ca, which produces locally [Ca(2+)] in the μM range on the inner side of the membrane, without significant [Ca(2+)] increase in the cytosol...
February 10, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28187982/the-renal-trpv4-channel-is-essential-for-adaptation-to-increased-dietary-potassium
#16
Mykola V Mamenko, Nabila Boukelmoune, Viktor N Tomilin, Oleg L Zaika, V Behrana Jensen, Roger G O'Neil, Oleh M Pochynyuk
To maintain potassium homeostasis, kidneys exert flow-dependent potassium secretion to facilitate kaliuresis in response to elevated dietary potassium intake. This process involves stimulation of calcium-activated large conductance maxi-K (BK) channels in the distal nephron, namely the connecting tubule and the collecting duct. Recent evidence suggests that the TRPV4 channel is a critical determinant of flow-dependent intracellular calcium elevations in these segments of the renal tubule. Here, we demonstrate that elevated dietary potassium intake (five percent potassium) increases renal TRPV4 mRNA and protein levels in an aldosterone-dependent manner and causes redistribution of the channel to the apical plasma membrane in native collecting duct cells...
February 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28177804/entry-infection-replication-and-egress-of-human-polyomaviruses-an-update
#17
Soumen Bhattacharjee, Sutanuka Chattaraj
Polyomaviruses (PyVs), belonging to the family Polyomaviridae, are a group of small, nonenveloped, double-stranded, circular DNA viruses widely distributed in the vertebrates. PyVs cause no apparent disease in adult laboratory mice but cause a wide variety of tumors when artificially inoculated into neonates or semipermissive animals. A few human PyVs, such as BK, JC, and Merkel cell PyVs, have been unequivocally linked to pathogenesis under conditions of immunosuppression. Infection is thought to occur early in life and persists for the lifespan of the host...
October 29, 2016: Canadian Journal of Microbiology
https://www.readbyqxmd.com/read/28168949/erg-28-controls-bk-channel-trafficking-in-the-er-to-regulate-synaptic-function-and-alcohol-response-in-c-elegans
#18
Kelly H Oh, James J Haney, Xiaohong Wang, Chiou-Fen Chuang, Janet E Richmond, Hongkyun Kim
Voltage- and calcium-dependent BK channels regulate calcium-dependent cellular events such as neurotransmitter release by limiting calcium influx. Their plasma membrane abundance is an important factor in determining BK current and thus regulation of calcium-dependent events. In C. elegans, we show that ERG-28, an endoplasmic reticulum (ER) membrane protein, promotes the trafficking of SLO-1 BK channels from the ER to the plasma membrane by shielding them from premature degradation. In the absence of ERG-28, SLO-1 channels undergo aspartic protease DDI-1-dependent degradation, resulting in markedly reduced expression at presynaptic terminals...
February 7, 2017: ELife
https://www.readbyqxmd.com/read/28165042/relationship-between-auxiliary-gamma-subunits-and-mallotoxin-on-bk-channel-modulation
#19
Xin Guan, Qin Li, Jiusheng Yan
The large-conductance, calcium- and voltage-activated K(+)(BK) channel consists of the pore-forming α subunits (BKα) and auxiliary subunits. The auxiliary γ1-3 subunits potently modulate the BK channel by shifting its voltage-dependence of channel activation toward the hyperpolarizing direction by approximately 145 mV (γ1), 100 mV (γ2), and 50 mV (γ3). Mallotoxin is a potent small-molecule BK channel activator. We analyzed the relationship between mallotoxin and the γ subunits in their BK channel-activating effects in membrane patches excised from HEK-293 cells...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28163105/nerve-growth-factor-derivative-ngf61-100-promotes-outgrowth-of-primary-sensory-neurons-with-reduced-signs-of-nociceptive-sensitization
#20
C Severini, P Petrocchi Passeri, M T Ciotti, F Florenzano, C Petrella, F Malerba, B Bruni, M D'Onofrio, I Arisi, R Brandi, R Possenti, P Calissano, A Cattaneo
Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease. However, the development of an NGF-based therapy is limited by its potent pain activity. We have developed a "painless" derivative form of human NGF (NGF61/100), characterized by identical neurotrophic properties but a reduced nociceptive sensitization activity in vivo. Here we characterized the response of rat dorsal root ganglia neurons (DRG) to the NGF derivative NGF61/100, in comparison to that of control NGF (NGF61), analyzing the expression of noxious pro-nociceptive mediators...
February 2, 2017: Neuropharmacology
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