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Potassium Channels

Ran Chai, Chengfen Xing, Dong Gao, Hongbo Yuan, Yong Zhan, Shu Wang
Spatiotemporal regulation of cellular functions provides a powerful strategy for understanding underlying mechanisms of cellular bioprocesses. Here, a strategy is reported to realize the remote control of the activities of potassium channels via photothermal inactivation of calmodulin (CaM) by using reduced graphene oxide decorated with calmodulin binding peptide (rGO-P) as the transducer with near-infrared light (NIR) irradiation. Upon NIR light irradiation, the CaM/Ca2+ bound to rGO-P is inactivated by the photothermal effect of rGO-P, resulting in the incapability of binding with Ca2+ ...
August 17, 2018: Advanced Healthcare Materials
Kelsey North, Shivantika Bisen, Alex M Dopico, Anna N Bukiya
Alcohol (ethanol) at physiologically relevant concentrations (<100 mM) constricts cerebral arteries via inhibition of voltage-/calcium-gated potassium channels of large conductance (BK) located in vascular smooth muscle (VSM). These channels consist of channel-forming slo1 (cbv1, KCNMA1) and accessory beta1 (KCNMB1) subunits. An increase in VSM cholesterol (CLR) via either dietary CLR intake or in vitro CLR enrichment was shown to protect against endothelium-independent, alcohol-induced constriction of cerebral arteries...
August 16, 2018: Journal of Pharmacology and Experimental Therapeutics
Pei-Chun Chen, Jing-Syuna Ruan, Sheng-Nan Wu
BACKGROUND/AIMS: Intermediate-conductance Ca2+-activated K+ (IKCa; KCa3.1 or KCNN4) channels affect the behaviors of central neurons including motor neurons. The mechanism through which neuronal differentiation is related to the activity of these channels remains largely unclear. METHODS: By using various molecular biology tools and electrophysiological measurements, we investigated possible changes in the activity of IKCa channels in a retinoic acid (RA)-induced differentiation process in motor neuron-like NSC-34 cells...
August 16, 2018: Cellular Physiology and Biochemistry
Robertino Dilena, Jacopo C DiFrancesco, Maria Virginia Soldovieri, Antonella Giacobbe, Paolo Ambrosino, Ilaria Mosca, Maria Albina Galli, Sophie Guez, Monica Fumagalli, Francesco Miceli, Dario Cattaneo, Francesca Darra, Elena Gennaro, Federico Zara, Pasquale Striano, Barbara Castellotti, Cinzia Gellera, Costanza Varesio, Pierangelo Veggiotti, Maurizio Taglialatela
Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare early-onset developmental epileptic encephalopathy resistant to anti-epileptic drugs. The most common cause for EIMFS is a gain-of-function mutation in the KCNT1 potassium channel gene, and treatment with the KCNT1 blocker quinidine has been suggested as a rational approach for seizure control in EIMFS patients. However, variable results on the clinical efficacy of quinidine have been reported. In the present study, we provide a detailed description of the clinical, genetic, in vitro, and in vivo electrophysiological profile and pharmacological responses to quinidine of 2 EIMFS unrelated patients with a heterozygous de novo KCNT1 mutation: c...
August 15, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Mun Fei Yam, Chu Shan Tan, Ruan Shibao
Orthosiphon stamineus Benth. (Lambiaceae) is an important traditional plant for the treatment of hypertension. Previous studies have demonstrated that the sinensetin content in O. stamineus is correlated with its vasorelaxant activity. However, there is still very little information regarding the vasorelaxant effect of sinensetin due to a lack of scientific studies. Therefore, the present study was designed to investigate the underlying mechanism of action of sinensetin in vasorelaxation using an in vitro precontraction aortic ring assay...
August 15, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Sundeep Malik, Emily Lambert, Junhui Zhang, Tong Wang, Heather Clark, Michael Cypress, Bruce Goldman, George A Porter, Salvador Pena, Wilson Nino, Daniel Gray
To better understand the role of the inward-rectifying K channel, Kir4.1 (KCNJ10), in the distal nephron, we initially studied a global Kir4.1 knock out mouse (gKO) which demonstrated the hypokalemia and hypomagnesemia seen in SeSAME/EAST syndrome and was associated with reduced Na/Cl cotransporter (NCC) expression. Lethality by ~3 wks, however, limits the usefulness of this model, so we developed a kidney specific Kir4.1 "knock down" mouse (ksKD) using a cadherin 16 promoter and Cre-loxP methodology...
August 15, 2018: American Journal of Physiology. Renal Physiology
Ancy Joseph, Tran Thi Thu Thuy, Le Tat Thanh, Masayoshi Okada
We screened a library of botanical compounds purified from plants of Vietnam for modulators of the activity of a two-pore domain K+ channel, TREK-1, and we identified a hydroxycoumarin-related compound, ostruthin, as an activator of this channel. Ostruthin increased whole-cell TREK-1 channel currents in 293T cells at a low concentration (EC50 = 5.3 μM), and also activity of the TREK-2 channel (EC50 = 3.7 mM). In contrast, ostruthin inhibited other K+ channels, e.g. human ether-à-go-go-related gene (HERG1), inward-rectifier (Kir2...
2018: PloS One
Doreen Matthies, Chanhyung Bae, Gilman Es Toombes, Tara Fox, Alberto Bartesaghi, Sriram Subramaniam, Kenton Jon Swartz
Voltage-activated potassium (Kv) channels open to conduct K+ ions in response to membrane depolarization, and subsequently enter non-conducting states through distinct mechanisms of inactivation. X-ray structures of detergent-solubilized Kv channels appear to have captured an open state even though a non-conducting C-type inactivated state would predominate in membranes in the absence of a transmembrane voltage. However, structures for a voltage-activated ion channel in a lipid bilayer environment have not yet been reported...
August 15, 2018: ELife
Michael G White, Brian N Mathur
Anterior cingulate cortex (ACC) input to the claustrum is required for top-down cognitive control of action. By virtue of its widespread cortical connectivity, the claustrum is anatomically situated to process and broadcast top-down signals from ACC to downstream cortices. To gain a deeper understanding of claustrum processing mechanisms, it is first critical to identify the projection neuron subtypes within claustrum, the intrinsic and extrinsic components regulating their firing, and the differential innervation of cortex by projection neuron subtypes...
August 14, 2018: Brain Structure & Function
Bruno Madio, Steve Peigneur, Yanni K Y Chin, Brett R Hamilton, Sónia Troeira Henriques, Jennifer J Smith, Ben Cristofori-Armstrong, Zoltan Dekan, Berin A Boughton, Paul F Alewood, Jan Tytgat, Glenn F King, Eivind A B Undheim
Sea anemone venoms have long been recognized as a rich source of peptides with interesting pharmacological and structural properties, but they still contain many uncharacterized bioactive compounds. Here we report the discovery, three-dimensional structure, activity, tissue localization, and putative function of a novel sea anemone peptide toxin that constitutes a new, sixth type of voltage-gated potassium channel (KV ) toxin from sea anemones. Comprised of just 17 residues, κ-actitoxin-Ate1a (Ate1a) is the shortest sea anemone toxin reported to date, and it adopts a novel three-dimensional structure that we have named the Proline-Hinged Asymmetric β-hairpin (PHAB) fold...
August 14, 2018: Cellular and Molecular Life Sciences: CMLS
José Ignacio Veytia-Bucheli, Juana María Jiménez-Vargas, Erika Isabel Melchy-Pérez, Monserrat Alba Sandoval-Hernández, Lourival Domingos Possani, Yvonne Rosenstein
BACKGROUND: In T cells, the Kv 1.3 and the KCa 3.1 potassium channels regulate the membrane potential and calcium homeostasis. Notably, during TEM cell activation, the number of Kv 1.3 channels on the cell membrane dramatically increases. Kv 1.3 blockade results in inhibition of Ca2+ signaling in TEM cells, thus eliciting an immunomodulatory effect. Among the naturally occurring peptides, the Vm24 toxin from the Mexican scorpion Vaejovis mexicanus is the most potent and selective Kv 1...
August 14, 2018: Cell Communication and Signaling: CCS
Thitaphat Ngernsutivorakul, Daniel Steyer, Alec C Valenta, Robert T Kennedy
An essential approach for in vivo chemical monitoring is to use sampling probes coupled with analytical methods; however, this method traditionally has limited spatial and temporal resolution. To address this problem, we have developed an analytical system that combines microfabricated push-pull sampling probes with droplet-based microfluidics. The microfabricated probe provides approximately 1000-fold better spatial resolution than common microdialysis probes. Microfabrication also facilitated integration of an extra channel into the probe for microinjection...
August 14, 2018: Analytical Chemistry
Nagisa Sugaya, Yasukazu Ogai, Yuzo Aikawa, Yosuke Yumoto, Mihoko Takahama, Miho Tanaka, Ayako Haraguchi, Mitsuru Umeno, Kazutaka Ikeda
AIM: This prospective, randomized, controlled, rater-blinded study investigated the effect of G protein-activated inwardly rectifying potassium (GIRK) channel inhibitor ifenprodil on alcohol use in patients with alcohol dependence. METHODS: The participants were 68 outpatients with alcohol dependence who were assigned to an ifenprodil group (administered 60 mg ifenprodil per day for 3 months) or control group (administered 600 mg ascorbic acid and calcium pantothenate per day for 3 months)...
March 2018: Neuropsychopharmacology reports
Hao Huang, Han Li, Kangpei Shi, Lei Wang, Xiaotong Zhang, Xiaobo Zhu
The aim of the current study was to explore the potential of TREK‑TRAAK two‑pore domain potassium (K2P) channels in protecting human retinal pigment epithelium (hRPE) cells against oxidative stress. hRPE cells were obtained from donors, and then cell identification and detection of the expression levels of TREK‑TRAAK K2P channels in hRPE cells were conducted. Subsequently, tert‑butyl hydroperoxide (t‑BH) was used to induce oxidative stress in hRPE cells. Docosahexaenoic acid (DHA) was used to stimulate and fluoxetine was used to inhibit the TREK‑TRAAK K2P channels...
August 8, 2018: International Journal of Molecular Medicine
Aravind S Kshatri, Alberto Gonzalez-Hernandez, Teresa Giraldez
Within the potassium ion channel family, calcium activated potassium (KCa ) channels are unique in their ability to couple intracellular Ca2+ signals to membrane potential variations. KCa channels are diversely distributed throughout the central nervous system and play fundamental roles ranging from regulating neuronal excitability to controlling neurotransmitter release. The physiological versatility of KCa channels is enhanced by alternative splicing and co-assembly with auxiliary subunits, leading to fundamental differences in distribution, subunit composition and pharmacological profiles...
2018: Frontiers in Molecular Neuroscience
John M Haynes, James N Selby, Isaiah Pl Abad, Teresa Vandekolk, Joan K Ho, Wai-Ling Lieuw, Katie Leach, Judith Savige, Sheetal Saini, Craig Fisher, Sharon Ricardo
Renal podocyte survival depends upon the dynamic regulation of a complex cell architecture that links glomerular basement membrane to integrins, ion channels and receptors. Alport syndrome is a heritable chronic kidney disease where mutations in α3, α4 or α5 collagen genes promote podocyte death. In rodent models of renal failure, activation of the calcium sensing receptor (CaSR) can protect podocytes from stress related death. In this study we assess CaSR function in podocyte-like cells from induced-pluripotent stem cells derived from two patients with Alport Syndrome (AS1 & AS2), a renal disease free individual (NHMC) and an immortalized podocyte-like (HIP) cell line...
August 13, 2018: Journal of Pharmacology and Experimental Therapeutics
Tianrong Yeo, Zhiyong Chen, Kok Pin Yong, Patricia Yut Wan Wong, Josiah Yui Huei Chai, Kevin Tan
BACKGROUND: To identify clinical and paraclinical differences between anti-voltage-gated potassium channel (VGKC)-complex seropositive patients with and without anti-leucine-rich glioma-inactivated protein 1 (LGI1)/contactin-associated protein-like 2 (CASPR2) antibodies (Abs). METHODS: We performed a retrospective analysis of 50 anti-VGKC-complex seropositive patients from January 2013 to September 2016, and tested them for anti-LGI1/CASPR2 Abs. Comparative analysis was performed between anti-LGI1/CASPR2 seropositive and 'double negative' patients...
August 15, 2018: Journal of the Neurological Sciences
Jiao Lu, Shan-Shan Pan, Qing-Tang Wang, Yang Yuan
The cardiac effects of exercise preconditioning (EP) are well established; however, the mechanisms involving cardiac ATP-sensitive potassium channel (KATP channel) subunits and autophagy are yet to be fully established. The present work aims to investigate the alterations of cardiac KATP channel subunits Kir6.2, SUR2A, and autophagy-related LC3 during the late cardioprotective phase of EP against exhaustive exercise-induced myocardial injury. Rats run on treadmill for four running time intervals, each with 10 minutes running and rest...
August 11, 2018: International Heart Journal
Lorenzo Camoni, Francesca Barbero, Patrizia Aducci, Massimo E Maffei
Biotic stresses induced by herbivores result in diverse physiological changes in plants. In the interaction between the Lima bean (Phaseolus lunatus) and the herbivore Spodoptera littoralis, the earliest event induced by feeding on leaves is the depolarization of the plasma membrane potential (Vm), which is the results of both mechanical damage and insect oral secretions (OS). Although this herbivore-induced Vm depolarization depends on a calcium-dependent opening of potassium channels, the attacked leaf remains depolarized for an extended period, which cannot be explained by the sole action of potassium channels...
2018: PloS One
Yang Xia, Lexin Xia, Lingyun Lou, Rui Jin, Huahao Shen, Wen Li
Chronic airway inflammatory diseases remain a major problem worldwide, such that there is a need for additional therapeutic targets and novel drugs. Transient receptor potential (TRP) channels are a group of non-selective cation channels expressed throughout the body that are regulated by various stimuli. TRP channels have been identified in numerous cell types in the respiratory tract, including sensory neurons, airway epithelial cells, airway smooth muscle cells, and fibroblasts. Different types of TRP channels induce cough in sensory neurons via the vagus nerve...
August 9, 2018: Lung
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