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https://www.readbyqxmd.com/read/27826710/the-action-of-smooth-muscle-cell-potassium-channels-in-the-pathology-of-pulmonary-arterial-hypertension
#1
REVIEW
Yasunobu Hayabuchi
Many different types of potassium channels with various functions exist in pulmonary artery smooth muscle cells, contributing to many physiological actions and pathological conditions. The deep involvement of these channels in the onset and exacerbation of pulmonary arterial hypertension (PAH) also continues to be revealed. In 2013, KCNK3 (TASK1), which encodes a type of two-pore domain potassium channel, was shown to be a predisposing gene for PAH by genetic mutation, and it was added to the PAH classification at the Fifth World Symposium on Pulmonary Hypertension (Nice International Conference)...
November 8, 2016: Pediatric Cardiology
https://www.readbyqxmd.com/read/27826078/participation-of-potassium-channels-in-the-antinociceptive-effect-of-docosahexaenoic-acid-in-the-rat-formalin-test
#2
Arizai Yolia Landa-Juárez, Mario I Ortiz, Gilberto Castañeda-Hernández, Aracely Evangelina Chávez-Piña
Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (PUFA) that has shown gastroprotective, cardioprotective, neuroprotective, anti-inflammatory and antinociceptive effects in different models. However, its action mechanism is still not well-defined. Reports indicate that some PUFAs regulate potassium (K(+)) channels in ventricular myocytes of rodents. As a result, the aim of this study was to evaluate the probable participation of K(+) channels in the antinociceptive effect of DHA. The rat paw 1% formalin test was used to assess nociception and antinociception...
November 6, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27763639/functional-kca1-1-channels-are-crucial-for-regulating-the-proliferation-migration-and-differentiation-of-human-primary-skeletal-myoblasts
#3
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/27497881/nitric-oxide-and-kir6-1-potassium-channel-mediate-isoquercitrin-induced-endothelium-dependent-and-independent-vasodilation-in-the-mesenteric-arterial-bed-of-rats
#4
Arquimedes Gasparotto Junior, Renê Dos Reis Piornedo, Jamil Assreuy, José Eduardo Da Silva-Santos
The vascular effect of flavonoid isoquercitrin was investigated in the perfused mesenteric vascular bed of rats. In preparations with functional endothelium isoquercitrin (100, 300 and 1000nmol) dose-dependently reduced the perfusion pressure by 13±2.2, 33±3.9, and 58±3.7mm Hg, respectively. Endothelium removal or inhibition of the nitric oxide synthase enzymes by l-NAME did not change the effects of 100 and 300 nmol isoquercitrin, but reduced by 30-40% the vasodilation induced by 1000 nmol isoquercitrin...
October 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27251429/erratum-to-different-expression-of-%C3%AE-subunits-of-the-kca1-1-channel-by-invasive-and-non-invasive-human-fibroblast-like-synoviocytes
#5
Zoltán Pethő, Mark R Tanner, Rajeev B Tajhya, Redwan Huq, Teresina Laragione, Gyorgy Panyi, Pércio S Gulko, Christine Beeton
No abstract text is available yet for this article.
2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27245839/kca1-1-a-calcium-activated-potassium-channel-subunit-alpha-1-is-targeted-by-mir-17-5p-and-modulates-cell-migration-in-malignant-pleural-mesothelioma
#6
Yuen Yee Cheng, Casey M Wright, Michaela B Kirschner, Marissa Williams, Kadir H Sarun, Vladimir Sytnyk, Iryna Leshchynska, J James Edelman, Michael P Vallely, Brian C McCaughan, Sonja Klebe, Nico van Zandwijk, Ruby C Y Lin, Glen Reid
BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive, locally invasive, cancer elicited by asbestos exposure and almost invariably a fatal diagnosis. To date, we are one of the leading laboratory that compared microRNA expression profiles in MPM and normal mesothelium samples in order to identify dysregulated microRNAs with functional roles in mesothelioma. We interrogated a significant collection of MPM tumors and normal pleural samples in our biobank in search for novel therapeutic targets...
2016: Molecular Cancer
https://www.readbyqxmd.com/read/27238271/developing-molecular-pharmacology-of-bk-channels-for-therapeutic-benefit
#7
G J Kaczorowski, M L Garcia
High conductance, calcium-activated potassium (BK) channels (KCa1.1) are important in regulating physiologic responses in many types of tissues and, as such, present opportunities for development of new therapeutic agents. Both channel agonists and inhibitors could have therapeutic utility, depending on medical application under consideration. However, characterization of molecular pharmacology of BK channels is incomplete and has been difficult to accomplish because of paucity of chemical leads that are acceptable templates for Medicinal Chemistry investigation...
2016: International Review of Neurobiology
https://www.readbyqxmd.com/read/27238263/protein-network-interacting-with-bk-channels
#8
H Kim, K H Oh
The large conductance, voltage- and calcium-dependent potassium BK channel, also termed BKCa, Maxi-K, KCa1.1, or SLO1, regulates a wide array of key biological processes that are mediated by calcium ions. This broad regulatory function of BK channels requires the interactions of BK channels with diverse sets of proteins that have different molecular or cellular functions. Proteins that interact with BK channels range from the auxiliary subunits of BK channels to cytoskeletal proteins responsible for BK channel trafficking and localization...
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
#9
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/27038377/the-modulation-of-potassium-channels-in-the-smooth-muscle-as-a-therapeutic-strategy-for-disorders-of-the-gastrointestinal-tract
#10
REVIEW
Diego Currò
Alterations of smooth muscle contractility contribute to the pathophysiology of important functional gastrointestinal disorders (FGIDs) such as functional dyspepsia and irritable bowel syndrome. Consequently, drugs that decrease smooth muscle contractility are effective treatments for these diseases. Smooth muscle contraction is mainly triggered by Ca(2+) influx through voltage-dependent channels located in the plasma membrane. Thus, the modulation of the membrane potential results in the regulation of Ca(2+) influx and cytosolic levels...
2016: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/26962098/hyperaldosteronism-after-decreased-renal-k-excretion-in-kcnmb2-knockout-mice
#11
Casper K Larsen, Iben S Jensen, Mads V Sorensen, Pauline I de Bruijn, Markus Bleich, Helle A Praetorius, Jens Leipziger
The kidney is the primary organ ensuring K(+) homeostasis. K(+) is secreted into the urine in the distal tubule by two mechanisms: by the renal outer medullary K(+) channel (Kir1.1) and by the Ca(2+)-activated K(+) channel (KCa1.1). Here, we report a novel knockout mouse of the β2-subunit of the KCa1.1 channel (KCNMB2), which displays hyperaldosteronism after decreased renal K(+) excretion. KCNMB2(-/-) mice displayed hyperaldosteronism, normal plasma K(+) concentration, and produced dilute urine with decreased K(+) concentration...
May 15, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/26883269/unique-expression-of-angiotensin-type-2-receptor-in-sex-specific-distribution-of-myelinated-ah-type-baroreceptor-neuron-contributing-to-sex-dimorphic-neurocontrol-of-circulation
#12
COMPARATIVE STUDY
Yang Liu, Jia-Ying Zhou, Yu-Hong Zhou, Di Wu, Jian-Li He, Li-Min Han, Xiao-Bo Liang, Lu-Qi Wang, Xiao-Long Lu, Hanying Chen, Guo-Fen Qiao, Weinian Shou, Bai-Yan Li
This study aims to understand the special expression patterns of angiotensin-II receptor (AT1R and AT2R) in nodose ganglia and nucleus of tractus solitary of baroreflex afferent pathway and their contribution in sex difference of neurocontrol of blood pressure regulation. In this regard, action potentials were recorded in baroreceptor neurons (BRNs) using whole-cell patch techniques; mRNA and protein expression of AT1R and AT2R in nodose ganglia and nucleus of tractus solitary were evaluated using real time-polymerase chain reaction, Western blot, and immunohistochemistry at both tissue and single-cell levels...
April 2016: Hypertension
https://www.readbyqxmd.com/read/26687482/synthetic-peptides-as-cgmp-independent-activators-of-cgmp-dependent-protein-kinase-i%C3%AE
#13
Thomas M Moon, Nathan R Tykocki, Jessica L Sheehe, Brent W Osborne, Werner Tegge, Joseph E Brayden, Wolfgang R Dostmann
PKG is a multifaceted signaling molecule and potential pharmaceutical target due to its role in smooth muscle function. A helix identified in the structure of the regulatory domain of PKG Iα suggests a novel architecture of the holoenzyme. In this study, a set of synthetic peptides (S-tides), derived from this helix, was found to bind to and activate PKG Iα in a cyclic guanosine monophosphate (cGMP)-independent manner. The most potent S-tide derivative (S1.5) increased the open probability of the potassium channel KCa1...
December 17, 2015: Chemistry & Biology
https://www.readbyqxmd.com/read/26352381/identification-and-characterization-of-gal-021-as-a-novel-breathing-control-modulator
#14
Francis J Golder, Scott Dax, Santhosh M Baby, Ryan Gruber, Toshinori Hoshi, Courtney Ideo, Andrew Kennedy, Sean Peng, Veljko Puskovic, David Ritchie, Richard Woodward, Robert L Wardle, Michael R Van Scott, James C Mannion, D Euan MacIntyre
BACKGROUND: The authors describe the preclinical pharmacological properties of GAL-021, a novel peripheral chemoreceptor modulator. METHODS: The ventilatory effects of GAL-021 were characterized using tracheal pneumotachometry (n = 4 to 6), plethysmography (n = 5 to 6), arterial blood gas analyses (n = 6 to 11), and nasal capnography (n = 3 to 4) in naive animals and those subjected to morphine-induced respiratory depression. Morphine analgesia in rats was evaluated by tail-flick test (n = 6)...
November 2015: Anesthesiology
https://www.readbyqxmd.com/read/26277325/reduction-in-renal-blood-flow-following-administration-of-norepinephrine-and-phenylephrine-in-septic-rats-treated-with-kir6-1-atp-sensitive-and-kca1-1-calcium-activated-k-channel-blockers
#15
Bruna da Rosa Maggi Sant'Helena, Karla L Guarido, Priscila de Souza, Sandra Crestani, J Eduardo da Silva-Santos
We evaluated the effects of K+ channel blockers in the vascular reactivity of in vitro perfused kidneys, as well as on the influence of vasoactive agents in the renal blood flow of rats subjected to the cecal ligation and puncture (CLP) model of sepsis. Both norepinephrine and phenylephrine had the ability to increase the vascular perfusion pressure reduced in kidneys of rats subjected to CLP at 18 h and 36 h before the experiments. The non-selective K+ channel blocker tetraethylammonium, but not the Kir6.1 blocker glibenclamide, normalized the effects of phenylephrine in kidneys from the CLP 18 h group...
October 15, 2015: European Journal of Pharmacology
https://www.readbyqxmd.com/read/26277265/unoprostone-activation-of-bk-kca1-1-channel-splice-variants
#16
Ling Yu, Amity F Eaton, Qiang Yue, Hui-Fang Bao, He-Ping Ma, John Cuppoletti, Douglas C Eaton
This investigation was conducted to study the relationship between intracellular Ca(2+) and activation of large conductance Ca(2+)-activated K(+) (BK) currents by unoprostone, the first synthetic docosanoid. We used HEK293 cells stably transfected with two BK channel splice variants, one sensitive to unoprostone and the other insensitive. We examined the effects of unoprostone on channel activity in excised inside-out patches and cell-attached patches. The half-maximal stimulation of the sensitive BK channels by Ca(2+) was shifted from 3...
November 2015: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/26219983/kca1-1-is-potential-marker-for-distinguishing-ah-type-baroreceptor-neurons-in-nts-and-contributes-to-sex-specific-presynaptic-neurotransmission-in-baroreflex-afferent-pathway
#17
Yu-Yao Zhang, Zhen-Yu Yan, Mei-Yu Qu, Xin-Jing Guo, Guo Li, Xiao-Long Lu, Yang Liu, Tao Ban, Hong-Li Sun, Guo-Fen Qiao, Bai-Yan Li
Sexual-dimorphic neurocontrol of circulation has been described in baroreflex due largely to the function of myelinated Ah-type baroreceptor neurons (BRNs, 1st-order) in nodose. However, it remains unclear if sex- and afferent-specific neurotransmission could also be observed in the central synapses within nucleus of solitary track (NTS, 2nd-order). According to the principle of no mixed neurotransmission among afferents and differentiation of Ah- and A-types to iberiotoxin (IbTX) observed in nodose, the 2nd-order Ah-type BRNs are highly expected...
September 14, 2015: Neuroscience Letters
https://www.readbyqxmd.com/read/25848765/high-expression-of-kca3-1-in-patients-with-clear-cell-renal-carcinoma-predicts-high-metastatic-risk-and-poor-survival
#18
Maj Rabjerg, Aida Oliván-Viguera, Lars Koch Hansen, Line Jensen, Linda Sevelsted-Møller, Steen Walter, Boye L Jensen, Niels Marcussen, Ralf Köhler
BACKGROUND: Ca2+-activated K+ channels have been implicated in cancer cell growth, metastasis, and tumor angiogenesis. Here we hypothesized that high mRNA and protein expression of the intermediate-conductance Ca2+-activated K+ channel, KCa3.1, is a molecular marker of clear cell Renal Cell Carcinoma (ccRCC) and metastatic potential and survival. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed channel expression by qRT-PCR, immunohistochemistry, and patch-clamp in ccRCC and benign oncocytoma specimens, in primary ccRCC and oncocytoma cell lines, as well as in two ccRCC cell lines (Caki-1 and Caki-2)...
2015: PloS One
https://www.readbyqxmd.com/read/25759640/action-potential-processing-in-a-detailed-purkinje-cell-model-reveals-a-critical-role-for-axonal-compartmentalization
#19
Stefano Masoli, Sergio Solinas, Egidio D'Angelo
The Purkinje cell (PC) is among the most complex neurons in the brain and plays a critical role for cerebellar functioning. PCs operate as fast pacemakers modulated by synaptic inputs but can switch from simple spikes to complex bursts and, in some conditions, show bistability. In contrast to original works emphasizing dendritic Ca-dependent mechanisms, recent experiments have supported a primary role for axonal Na-dependent processing, which could effectively regulate spike generation and transmission to deep cerebellar nuclei (DCN)...
2015: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/25545736/p2y%C3%A2-receptor-activation-decreases-blood-pressure-via-intermediate-conductance-potassium-channels-and-connexin-37
#20
J A Dominguez Rieg, J M Burt, P Ruth, T Rieg
AIMS: Nucleotides are important paracrine regulators of vascular tone. We previously demonstrated that activation of P2Y₂ receptors causes an acute, NO-independent decrease in blood pressure, indicating this signalling pathway requires an endothelial-derived hyperpolarization (EDH) response. To define the mechanisms by which activation of P2Y₂ receptors initiates EDH and vasodilation, we studied intermediate-conductance (KCa3.1, expressed in endothelial cells) and big-conductance potassium channels (KCa1...
March 2015: Acta Physiologica
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