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https://www.readbyqxmd.com/read/28090300/bk-channels-in-rat-and-human-pulmonary-smooth-muscle-cells-are-bk%C3%AE-%C3%AE-1-functional-complexes-lacking-the-oxygen-sensitive-stress-axis-regulated-exon-insert
#1
Neil D Detweiler, Li Song, Samantha J McClenahan, Rachel J Versluis, Sujay V Kharade, Richard C Kurten, Sung W Rhee, Nancy J Rusch
A loss of K(+) efflux in pulmonary arterial smooth muscle cells (PASMCs) contributes to abnormal vasoconstriction and PASMC proliferation during pulmonary hypertension (PH). Activation of high-conductance Ca(2+)-activated (BK) channels represents a therapeutic strategy to restore K(+) efflux to the affected PASMCs. However, the properties of BK channels in PASMCs-including sensitivity to BK channel openers (BKCOs)-are poorly defined. The goal of this study was to compare the properties of BK channels between PASMCs of normoxic (N) and chronic hypoxic (CH) rats and then explore key findings in human PASMCs...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28041976/moving-pieces-in-a-cryptomic-puzzle-cryptide-from-tityus-serrulatus-ts3-nav-toxin-as-potential-agonist-of-muscarinic-receptors
#2
Cibele Rocha-Resende, Nádia Miricéia Leão, Maria Elena de Lima, Robson Augusto Santos, Adriano Monteiro de Castro Pimenta, Thiago Verano-Braga
Cryptome is as a subset of a given proteome containing bioactive cryptides embedded in larger peptides or proteins. We pinpointed a striking sequence similarity between two peptides from the Tityus serrulatus venom: Ts10 (KKDGYPVEYDRAY) and the N-terminal of Ts3 (KKDGYPVEYDNCAY). Ts3 (former Tityustoxin or TsIV) is an α-neurotoxin acting on voltage-gated sodium channels while Ts10 (former Peptide T) is a bradykinin-potentiating peptide and was originally reported as inhibitor of the angiotensin-converting enzyme (ACEi)...
December 29, 2016: Peptides
https://www.readbyqxmd.com/read/28026020/low-pho-boosts-burst-firing-and-catecholamine-release-by-blocking-task-1-and-bk-channels-while-preserving-cav1-channels-in-mouse-chromaffin-cells
#3
Laura Guarina, David H F Vandael, Valentina Carabelli, Emilio Carbone
Mouse chromaffin cells (MCCs) generate action potential (AP) firing that regulates the Ca(2+) -dependent release of catecholamines (CAs). Recent findings indicate that MCCs possess a variety of spontaneous firing modes that span from the common "tonic-irregular" to the less frequent "burst" firing. This latter is evident in a small fraction of MCCs but occurs regularly when Nav1.3/1.7 channels are made less available or when the Slo1β2-subunit responsible for BK channel inactivation is deleted. Burst firing causes massive increases of Ca(2+) -entry and potentiates CA release ∼3...
December 27, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/28025959/hypokalemia-associated-with-acute-colonic-pseudo-obstruction-in-an-esrd-patient
#4
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/28012000/differential-distribution-and-functional-impact-of-bk-channel-beta1-subunits-across-mesenteric-coronary-and-different-cerebral-arteries-of-the-rat
#5
Guruprasad Kuntamallappanavar, Shivantika Bisen, Anna N Bukiya, Alex M Dopico
Large conductance, Ca(2+)i- and voltage-gated K(+) (BK) channels regulate myogenic tone and, thus, arterial diameter. In smooth muscle (SM), BK channels include channel-forming α and auxiliary β1 subunits. BK β1 increases the channel's Ca(2+) sensitivity, allowing BK channels to negatively feedback on depolarization-induced Ca(2+) entry, oppose SM contraction and favor vasodilation. Thus, endothelial-independent vasodilation can be evoked though targeting of SM BK β1 by endogenous ligands, including lithocholate (LCA)...
December 24, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27999123/early-alterations-of-hippocampal-neuronal-firing-induced-by-abeta42
#6
Daniela Gavello, Chiara Calorio, Claudio Franchino, Federico Cesano, Valentina Carabelli, Emilio Carbone, Andrea Marcantoni
We studied the effect of Amyloid β 1-42 oligomers (Abeta42) on Ca(2+) dependent excitability profile of hippocampal neurons. Abeta42 is one of the Amyloid beta peptides produced by the proteolytic processing of the amyloid precursor protein and participates in the initiating event triggering the progressive dismantling of synapses and neuronal circuits. Our experiments on cultured hippocampal network reveal that Abeta42 increases intracellular Ca(2+) concentration by 46% and inhibits firing discharge by 19%...
December 19, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27989457/bk-channels-are-required-for-multisensory-plasticity-in-the-oculomotor-system
#7
Alexandra B Nelson, Michael Faulstich, Setareh Moghadam, Kimberly Onori, Andrea Meredith, Sascha du Lac
Neural circuits are endowed with several forms of intrinsic and synaptic plasticity that could contribute to adaptive changes in behavior, but circuit complexities have hindered linking specific cellular mechanisms with their behavioral consequences. Eye movements generated by simple brainstem circuits provide a means for relating cellular plasticity to behavioral gain control. Here we show that firing rate potentiation, a form of intrinsic plasticity mediated by reductions in BK-type calcium-activated potassium currents in spontaneously firing neurons, is engaged during optokinetic reflex compensation for inner ear dysfunction...
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/27982688/aerobic-exercise-of-low-to-moderate-intensity-corrects-unequal-changes-in-bk-ca-subunit-expression-in-the-mesenteric-arteries-of-spontaneously-hypertensive-rats
#8
Yanyan Zhang, Yu Chen, Lin Zhang, Ni Lu, Lijun Shi
Accumulating evidence indicates that hypertension is associated with "ion channel remodeling" of vascular smooth muscle cells (VSMCs). The objective of this study was to determine the effects of exercise intensity/volume on hypertension-associated changes in large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels in mesenteric arteries (MAs) from spontaneously hypertensive rats (SHR). Male SHRs were randomly assigned to three groups: a low-intensity aerobic exercise group (SHR-L: 14 m/min), a moderate-intensity aerobic exercise group (SHR-M: 20 m/min), and a sedentary group (SHR)...
December 16, 2016: Physiological Research
https://www.readbyqxmd.com/read/27960620/the-goslo-family-of-bk-channel-activators-a-no-go-for-%C3%AE-subunits
#9
Teresa Giraldez
No abstract text is available yet for this article.
December 14, 2016: Channels
https://www.readbyqxmd.com/read/27918826/long-term-protection-of-genetically-ablated-rabbit-retinal-degeneration-by-sustained-transscleral-unoprostone-delivery
#10
Nobuhiro Nagai, Eri Koyanagi, Yasuko Izumida, Junjun Liu, Aya Katsuyama, Hirokazu Kaji, Matsuhiko Nishizawa, Noriko Osumi, Mineo Kondo, Hiroko Terasaki, Yukihiko Mashima, Toru Nakazawa, Toshiaki Abe
Purpose: To evaluate the long-term protective effects of transscleral unoprostone (UNO) against retinal degeneration in transgenic (Tg) rabbits (Pro347Leu rhodopsin mutation). Methods: The UNO release devices (URDs) were implanted into the sclerae of Tg rabbits and ERG, optical coherence tomography (OCT), and ophthalmic examinations were conducted for 40 weeks. Unoprostone metabolites in retina, choroid/RPE, aqueous humor, and plasma from wild-type (Wt) rabbits were measured using liquid chromatography-tandem mass spectrometry...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27898416/sgk3-sensitivity-of-large-conductance-ca2-activated-k-channel
#11
Musaab Ahmed, Myriam Fezai, Florian Lang
BACKGROUND/AIMS: Large conductance Ca2+-activated K+ channels (maxi K+ channels or BK channels) are rapidly activated by increase of cytosolic Ca2+ activity. The channels participate in the regulation of diverse functions including neuronal excitation and cell volume. The BK channels may be modified by kinases. Channel regulating kinases include the serum & glucocorticoid inducible kinase 3 (SGK3). The present study explored whether SGK3 modifies the activity of BK channels. METHODS: cRNA encoding the Ca2+ insensitive BK channel mutant BKM513I+Δ899-903 was injected into Xenopus laevis oocytes without or with additional injection of cRNA encoding wild-type SGK3, constitutively active S419DSGK3, or catalytically inactive K191NSGK3...
November 30, 2016: Neuro-Signals
https://www.readbyqxmd.com/read/27872281/interactions-of-divalent-cations-with-calcium-binding-sites-of-bk-channels-reveal-independent-motions-within-the-gating-ring
#12
Pablo Miranda, Teresa Giraldez, Miguel Holmgren
Large-conductance voltage- and calcium-activated K(+) (BK) channels are key physiological players in muscle, nerve, and endocrine function by integrating intracellular Ca(2+) and membrane voltage signals. The open probability of BK channels is regulated by the intracellular concentration of divalent cations sensed by a large structure in the BK channel called the "gating ring," which is formed by four tandems of regulator of conductance for K(+) (RCK1 and RCK2) domains. In contrast to Ca(2+) that binds to both RCK domains, Mg(2+), Cd(2+), or Ba(2+) interact preferentially with either one or the other...
December 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27872049/contribution-of-kv1-5-channel-to-h2o2-induced-human-arteriolar-dilation-and-its-modulation-by-coronary-artery-disease
#13
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 BKCa channels in subjects with coronary artery disease (CAD), but its mechanisms of action in subjects without CAD (non-CAD) as compared to 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...
November 21, 2016: Circulation Research
https://www.readbyqxmd.com/read/27856251/local-calcium-signalling-is-mediated-by-mechanosensitive-ion-channels-in-mesenchymal-stem-cells
#14
Vladislav I Chubinskiy-Nadezhdin, Valeria Y Vasileva, Natalia A Pugovkina, Irina O Vassilieva, Elena A Morachevskaya, Nikolay N Nikolsky, Yuri A Negulyaev
Mechanical forces are implicated in key physiological processes in stem cells, including proliferation, differentiation and lineage switching. To date, there is an evident lack of understanding of how external mechanical cues are coupled with calcium signalling in stem cells. Mechanical reactions are of particular interest in adult mesenchymal stem cells because of their promising potential for use in tissue remodelling and clinical therapy. Here, single channel patch-clamp technique was employed to search for cation channels involved in mechanosensitivity in mesenchymal endometrial-derived stem cells (hMESCs)...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27849612/atomic-determinants-of-bk-channel-activation-by-polyunsaturated-fatty-acids
#15
Yutao Tian, Marius Aursnes, Trond Vidar Hansen, Jørn Eivind Tungen, Jason D Galpin, Lilia Leisle, Christopher A Ahern, Rong Xu, Stefan H Heinemann, Toshinori Hoshi
Docosahexaenoic acid (DHA), a polyunsaturated ω-3 fatty acid enriched in oily fish, contributes to better health by affecting multiple targets. Large-conductance Ca(2+)- and voltage-gated Slo1 BK channels are directly activated by nanomolar levels of DHA. We investigated DHA-channel interaction by manipulating both the fatty acid structure and the channel composition through the site-directed incorporation of unnatural amino acids. Electrophysiological measurements show that the para-group of a Tyr residue near the ion conduction pathway has a critical role...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27834847/astaxanthin-and-docosahexaenoic-acid-reverse-the-toxicity-of-the-maxi-k-bk-channel-antagonist-mycotoxin-penitrem-a
#16
Amira A Goda, Khayria M Naguib, Magdy M Mohamed, Hassan A Amra, Somaia A Nada, Abdel-Rahman B Abdel-Ghaffar, Chris R Gissendanner, Khalid A El Sayed
Penitrem A (PA) is a food mycotoxin produced by several terrestrial and few marine Penicillium species. PA is a potent tremorgen through selective antagonism of the calcium-dependent potassium BK (Maxi-K) channels. Discovery of natural products that can prevent the toxic effects of PA is important for food safety. Astaxanthin (AST) is a marine natural xanthophyll carotenoid with documented antioxidant activity. Unlike other common antioxidants, AST can cross blood brain barriers (BBBs), inducing neuroprotective effects...
November 9, 2016: Marine Drugs
https://www.readbyqxmd.com/read/27827370/ethanol-sensitive-pacemaker-neurons-in-the-mouse-external-globus-pallidus
#17
Karina P Abrahao, Jessica H Chancey, C Savio Chan, David M Lovinger
Although ethanol is one of the most widely used drugs, we still lack a full understanding of which neuronal subtypes are affected by this drug. Pacemaker neurons exert powerful control over brain circuit function, but little is known about ethanol effects on these types of neurons. Neurons in the external globus pallidus (GPe) generate pacemaker activity that controls basal ganglia, circuitry associated with habitual and compulsive drug use. We performed patch-clamp recordings from GPe neurons and found that bath application of ethanol dose-dependently decreased the firing rate of low-frequency GPe neurons, but did not alter the firing of high-frequency neurons...
December 14, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27812391/use-of-aldosterone-antagonist-to-treat-diarrhea-and-hypokalemia-of-ogilvie-s-syndrome
#18
Pradhum Ram, Abhinav Goyal, Marvin Lu, Joshua Sloan, William McElhaugh
Ogilvie's syndrome (OS) is a functional obstruction of the bowel due to an autonomic imbalance. It often presents with diarrhea and is associated with hypokalemia. We present a case of a 70-year-old male who developed severe abdominal distension, watery diarrhea, and persistent hypokalemia status after left hip arthroplasty after suffering from a femoral neck fracture due to a fall and was diagnosed with OS. The persistent hypokalemia was slow to improve despite aggressive repletion because of the high potassium losses in the stool...
2016: Case Reports in Gastrointestinal Medicine
https://www.readbyqxmd.com/read/27807200/molecular-determinants-of-bk-channel-functional-diversity-and-functioning
#19
REVIEW
Ramon Latorre, Karen Castillo, Willy Carrasquel-Ursulaez, Romina V Sepulveda, Fernando Gonzalez-Nilo, Carlos Gonzalez, Osvaldo Alvarez
Large-conductance Ca(2+)- and voltage-activated K(+) (BK) channels play many physiological roles ranging from the maintenance of smooth muscle tone to hearing and neurosecretion. BK channels are tetramers in which the pore-forming α subunit is coded by a single gene (Slowpoke, KCNMA1). In this review, we first highlight the physiological importance of this ubiquitous channel, emphasizing the role that BK channels play in different channelopathies. We next discuss the modular nature of BK channel-forming protein, in which the different modules (the voltage sensor and the Ca(2+) binding sites) communicate with the pore gates allosterically...
January 2017: Physiological Reviews
https://www.readbyqxmd.com/read/27806944/the-mechanosensitive-bk%C3%AE-%C3%AE-1-channel-localizes-to-cilia-of-principal-cells-in-rabbit-cortical-collecting-duct-ccd
#20
Rolando Carrisoza-Gaytán, Lijun Wang, Carlos Schreck, Thomas R Kleyman, Wen-Hui Wang, Lisa M Satlin
Within the CCD of the distal nephron of the rabbit, the BK (maxi K) channel mediates Ca(2+)- and/or stretch-dependent flow-induced K(+) secretion (FIKS) and contributes to K(+) adaptation in response to dietary K(+) loading. An unresolved question is whether BK channels in intercalated cells (ICs) and/or principal cells (PCs) in the CCD mediate these K(+) secretory processes. In support of a role for ICs in FIKS is the higher density of immunoreactive apical BKα (pore-forming subunit) and functional BK channel activity than detected in PCs, and an increase in IC BKα expression in response to a high-K(+) diet...
January 1, 2017: American Journal of Physiology. Renal Physiology
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