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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/28246116/understanding-the-conformational-motions-of-rck-gating-rings
#2
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...
April 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28177804/entry-infection-replication-and-egress-of-human-polyomaviruses-an-update
#3
REVIEW
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...
March 2017: Canadian Journal of Microbiology
https://www.readbyqxmd.com/read/28163105/nerve-growth-factor-derivative-ngf61-100-promotes-outgrowth-of-primary-sensory-neurons-with-reduced-signs-of-nociceptive-sensitization
#4
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
https://www.readbyqxmd.com/read/28133948/maternal-high-salt-diet-altered-adenosine-mediated-vasodilatation-via-pka-bk-channel-pathway-in-offspring-rats
#5
Jue Wu, Na Li, Yanping Liu, Weisheng Li, Axin He, Di Zhu, Xueqin Feng, Bailin Liu, Ruixiu Shi, Yujuan Zhang, Juanxiu Lv, Zhice Xu
SCOPE: High salt (HS) diets are related to cardiovascular diseases, and prenatal HS was suggested to increase risks of coronary artery diseases in the offspring. This study tested the hypothesis that prenatal HS may influence Adenosine-induced vasodilatation via protein kinase A (PKA) pathway in coronary arteries. METHODS AND RESULTS: Sprague-Dawley rats were fed with 8% salt diet for gestation, the control was fed with 0.3% salt diet. Coronary arteries from male adult offspring were tested for K(+) channels and Adenosine signal pathways...
January 29, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28025959/hypokalemia-associated-with-acute-colonic-pseudo-obstruction-in-an-esrd-patient
#6
Khaled Boobés, Robert M Rosa, Daniel Batlle
Ogilvie's syndrome, or acute colonic pseudo-obstruction, is characterized by massive dilation of the colon without mechanical obstruction. Water and electrolytes often can be sequestered in the dilated intestinal loops resulting in profuse and watery diarrhea as well as hypokalemia. We report an anuric, end-stage renal disease (ESRD) patient undergoing peritoneal dialysis (PD) who developed acute colonic pseudo-obstruction causing a prolonged hospitalization. He also developed severe hypokalemia with a serum potassium (K+) as low as 2...
December 27, 2016: Clinical Nephrology
https://www.readbyqxmd.com/read/27872049/contribution-of-kv1-5-channel-to-hydrogen-peroxide-induced-human-arteriolar-dilation-and-its-modulation-by-coronary-artery-disease
#7
Yoshinori Nishijima, Sheng Cao, Dawid S Chabowski, Ankush Korishettar, Alyce Ge, Xiaodong Zheng, Rodney Sparapani, David D Gutterman, David X Zhang
RATIONALE: Hydrogen peroxide (H2O2) regulates vascular tone in the human microcirculation under physiological and pathophysiological conditions. It dilates arterioles by activating large-conductance Ca(2+)-activated K(+) channels in subjects with coronary artery disease (CAD), but its mechanisms of action in subjects without CAD (non-CAD) when compared with those with CAD remain unknown. OBJECTIVE: We hypothesize that H2O2-elicited dilation involves different K(+) channels in non-CAD versus CAD, resulting in an altered capacity for vasodilation during disease...
February 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/27763639/functional-kca1-1-channels-are-crucial-for-regulating-the-proliferation-migration-and-differentiation-of-human-primary-skeletal-myoblasts
#8
Rajeev B Tajhya, Xueyou Hu, Mark R Tanner, Redwan Huq, Natee Kongchan, Joel R Neilson, George G Rodney, Frank T Horrigan, Lubov T Timchenko, Christine Beeton
Myoblasts are mononucleated precursors of myofibers; they persist in mature skeletal muscles for growth and regeneration post injury. During myotonic dystrophy type 1 (DM1), a complex autosomal-dominant neuromuscular disease, the differentiation of skeletal myoblasts into functional myotubes is impaired, resulting in muscle wasting and weakness. The mechanisms leading to this altered differentiation are not fully understood. Here, we demonstrate that the calcium- and voltage-dependent potassium channel, KCa1...
October 20, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27690717/the-glycosylation-of-the-extracellular-loop-of-%C3%AE-2-subunits-diversifies-functional-phenotypes-of-bk-channels
#9
Zhi-Gang Huang, Hao-Wen Liu, Zhen-Zhen Yan, Sheng Wang, Lu-Yang Wang, Jiu-Ping Ding
Large-conductance Ca(2+)- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit. Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels. Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119)...
March 4, 2017: Channels
https://www.readbyqxmd.com/read/27670435/bk-channel-agonist-represents-a-potential-therapeutic-approach-for-lysosomal-storage-diseases
#10
Xi Zoë Zhong, Xue Sun, Qi Cao, Gaofeng Dong, Raphael Schiffmann, Xian-Ping Dong
Efficient lysosomal Ca(2+) release plays an essential role in lysosomal trafficking. We have recently shown that lysosomal big conductance Ca(2+)-activated potassium (BK) channel forms a physical and functional coupling with the lysosomal Ca(2+) release channel Transient Receptor Potential Mucolipin-1 (TRPML1). BK and TRPML1 forms a positive feedback loop to facilitate lysosomal Ca(2+) release and subsequent lysosome membrane trafficking. However, it is unclear whether the positive feedback mechanism is common for other lysosomal storage diseases (LSDs) and whether BK channel agonists rescue abnormal lysosomal storage in LSDs...
September 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27619153/binaural-blood-flow-control-by-astrocytes-listening-to-synapses-and-the-vasculature
#11
Anusha Mishra
Astrocytes are the most common glial cells in the brain with fine processes and endfeet that intimately contact both neuronal synapses and the cerebral vasculature. They play an important role in mediating neurovascular coupling (NVC) via several astrocytic Ca(2+) -dependent signalling pathways such as K(+) release through BK channels, and the production and release of arachidonic acid metabolites. They are also involved in maintaining the resting tone of the cerebral vessels by releasing ATP and COX-1 derivatives...
March 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/27445840/large-conductance-calcium-activated-potassium-channels-in-glomerulus-from-cell-signal-integration-to-disease
#12
REVIEW
Jie Tao, Zhen Lan, Yunman Wang, Hongya Hei, Lulu Tian, Wanma Pan, Xuemei Zhang, Wen Peng
Large-conductance calcium-activated potassium (BK) channels are currently considered as vital players in a variety of renal physiological processes. In podocytes, BK channels become active in response to stimuli that increase local cytosolic Ca(2+), possibly secondary to activation of slit diaphragm TRPC6 channels by chemical or mechanical stimuli. Insulin increases filtration barrier permeability through mobilization of BK channels. In mesangial cells, BK channels co-expressed with β1 subunits act as a major component of the counteractive response to contraction in order to regulate glomerular filtration...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27440457/differential-efficacy-of-goslo-sr-compounds-on-bk%C3%AE-and-bk%C3%AE-%C3%AE-1-4-channels
#13
Aravind S Kshatri, Qin Li, Jiusheng Yan, Roddy J Large, Gerard P Sergeant, Noel G McHale, Keith D Thornbury, Mark A Hollywood
Large conductance, voltage and Ca(2+) activated K(+) channels (BK channels) are abundantly expressed throughout the body and are important regulators of smooth muscle tone and neuronal excitability. Their dysfunction is implicated in various diseases including overactive bladder, hypertension and erectile dysfunction. Therefore, BK channel openers bear significant therapeutic potential to treat the above diseases. GoSlo-SR compounds were designed to be potent and efficacious BK channel openers. Although their structural activity relationships, activation in both BKα and BKαβ channels and the hypothetical mode of action of these compounds has been studied in detail in recent years, their effectiveness to open the BKαγ channels still remains unexplored...
January 2, 2017: Channels
https://www.readbyqxmd.com/read/27329042/bk-knockout-by-talen-mediated-gene-targeting-in-osteoblasts-kcnma1-determines-the-proliferation-and-differentiation-of-osteoblasts
#14
Hongya Hei, Jianjun Gao, Jibin Dong, Jie Tao, Lulu Tian, Wanma Pan, Hongyu Wang, Xuemei Zhang
Large conductance calcium-activated potassium (BK) channels participate in many important physiological functions in excitable tissues such as neurons, cardiac and smooth muscles, whereas the knowledge of BK channels in bone tissues and osteoblasts remains elusive. To investigate the role of BK channels in osteoblasts, we used transcription activator-like effector nuclease (TALEN) to establish a BK knockout cell line on rat ROS17/2.8 osteoblast, and detected the proliferation and mineralization of the BK-knockout cells...
July 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27238265/modulation-of-bk-channels-by-small-endogenous-molecules-and-pharmaceutical-channel-openers
#15
T Hoshi, S H Heinemann
Voltage- and Ca(2+)-activated K(+) channels of big conductance (BK channels) are abundantly found in various organs and their relevance for smooth muscle tone and neuronal signaling is well documented. Dysfunction of BK channels is implicated in an array of human diseases involving many organs including the nervous, pulmonary, cardiovascular, renal, and urinary systems. In humans a single gene (KCNMA1) encodes the pore-forming α subunit (Slo1) of BK channels, but the channel properties are variable because of alternative splicing, tissue- and subcellular-specific auxiliary subunits (β, γ), posttranslational modifications, and a multitude of endogenous signaling molecules directly affecting the channel function...
2016: International Review of Neurobiology
https://www.readbyqxmd.com/read/27238262/posttranscriptional-and-posttranslational-regulation-of-bk-channels
#16
M J Shipston, L Tian
Large conductance calcium- and voltage-activated potassium (BK) channels are ubiquitously expressed and play an important role in the regulation of an eclectic array of physiological processes. Their diverse functional role requires channels with a wide variety of properties even though the pore-forming α-subunit is encoded by a single gene, KCNMA1. To achieve this, BK channels exploit some of the most fundamental posttranscriptional and posttranslational mechanisms that allow proteomic diversity to be generated from a single gene...
2016: International Review of Neurobiology
https://www.readbyqxmd.com/read/27165430/different-expression-of-%C3%AE-subunits-of-the-kca1-1-channel-by-invasive-and-non-invasive-human-fibroblast-like-synoviocytes
#17
Zoltán Pethő, Mark R Tanner, Rajeev B Tajhya, Redwan Huq, Teresina Laragione, Gyorgy Panyi, Pércio S Gulko, Christine Beeton
BACKGROUND: Fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA-FLS) contribute to joint inflammation and damage characteristic of the disease. RA-FLS express KCa1.1 (BK, Slo1, MaxiK, KCNMA1) as their major plasma membrane potassium channel. Blocking KCa1.1 reduces the invasive phenotype of RA-FLS and attenuates disease severity in animal models of RA. This channel has therefore emerged as a promising therapeutic target in RA. However, the pore-forming α subunit of KCa1.1 is widely distributed in the body, and blocking it induces severe side effects, thus limiting its value as a therapeutic target...
2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27116676/membrane-channel-gene-expression-in-human-costal-and-articular-chondrocytes
#18
A Asmar, R Barrett-Jolley, A Werner, R Kelly, M Stacey
Chondrocytes are the uniquely resident cells found in all types of cartilage and key to their function is the ability to respond to mechanical loads with changes of metabolic activity. This mechanotransduction property is, in part, mediated through the activity of a range of expressed transmembrane channels; ion channels, gap junction proteins, and porins. Appropriate expression of ion channels has been shown essential for production of extracellular matrix and differential expression of transmembrane channels is correlated to musculoskeletal diseases such as osteoarthritis and Albers-Schönberg...
April 2, 2016: Organogenesis
https://www.readbyqxmd.com/read/27115952/airway-hydration-apical-k-secretion-and-the-large-conductance-ca-2-activated-and-voltage-dependent-potassium-bk-channel
#19
Adrian Kis, Stefanie Krick, Nathalie Baumlin, Matthias Salathe
Large-conductance, calcium-activated, and voltage-gated K(+) (BK) channels are expressed in many tissues of the human body, where they play important roles in signaling not only in excitable but also in nonexcitable cells. Because BK channel properties are rendered in part by their association with four β and four γ subunits, their channel function can differ drastically, depending on in which cellular system they are expressed. Recent studies verify the importance of apically expressed BK channels for airway surface liquid homeostasis and therefore of their significant role in mucociliary clearance...
April 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/27105427/reconstruction-of-cell-surface-densities-of-ion-pumps-exchangers-and-channels-from-mrna-expression-conductance-kinetics-whole-cell-calcium-and-current-clamp-voltage-recordings-with-an-application-to-human-uterine-smooth-muscle-cells
#20
Jolene Atia, Conor McCloskey, Anatoly S Shmygol, David A Rand, Hugo A van den Berg, Andrew M Blanks
Uterine smooth muscle cells remain quiescent throughout most of gestation, only generating spontaneous action potentials immediately prior to, and during, labor. This study presents a method that combines transcriptomics with biophysical recordings to characterise the conductance repertoire of these cells, the 'conductance repertoire' being the total complement of ion channels and transporters expressed by an electrically active cell. Transcriptomic analysis provides a set of potential electrogenic entities, of which the conductance repertoire is a subset...
April 2016: PLoS Computational Biology
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