Channel Interaction (channel + interaction)

Distribution by Scientific Domains


Selected Abstracts


Casein kinase 2 specifically binds to and phosphorylates the carboxy termini of ENaC subunits

FEBS JOURNAL, Issue 18 2002
Haikun Shi
A number of findings have suggested the involvement of protein phosphorylation in the regulation of the epithelial Na+ channel (ENaC). A recent study has demonstrated that the C tails of the , and , subunits of ENaC are subject to phosphorylation by at least three protein kinases [Shi, H., Asher, C., Chigaev, A., Yung, Y., Reuveny, E., Seger, R. & Garty, H. (2002) J. Biol. Chem. 277, 13539,13547]. One of them was identified as ERK which phosphorylates ,T613 and ,T623 and affects the channel interaction with Nedd4. The current study identifies a second protein kinase as casein kinase 2 (CK2), or CK-2-like kinase. It phosphorylates ,S631, a well-conserved serine on the , subunit. Such phosphorylation is observed both in vitro using glutathione-S-transferase,ENaC fusion proteins and in vivo in ENaC-expressing Xenopus oocytes. The , subunit is weakly phosphorylated by this protein kinase on another residue (,T599), and the C tail of , is not significantly phosphorylated by this kinase. Thus, CK2 may be involved in the regulation of the epithelial Na+ channel. [source]


Collation, assessment and analysis of literature in vitro data on hERG receptor blocking potency for subsequent modeling of drugs' cardiotoxic properties

JOURNAL OF APPLIED TOXICOLOGY, Issue 3 2009
Sebastian Polak
Abstract The assessment of the torsadogenic potency of a new chemical entity is a crucial issue during lead optimization and the drug development process. It is required by the regulatory agencies during the registration process. In recent years, there has been a considerable interest in developing in silico models, which allow prediction of drug,hERG channel interaction at the early stage of a drug development process. The main mechanism underlying an acquired QT syndrome and a potentially fatal arrhythmia called torsades de pointes is the inhibition of potassium channel encoded by hERG (the human ether-a-go-go-related gene). The concentration producing half-maximal block of the hERG potassium current (IC50) is a surrogate marker for proarrhythmic properties of compounds and is considered a test for cardiac safety of drugs or drug candidates. The IC50 values, obtained from data collected during electrophysiological studies, are highly dependent on experimental conditions (i.e. model, temperature, voltage protocol). For the in silico models' quality and performance, the data quality and consistency is a crucial issue. Therefore the main objective of our work was to collect and assess the hERG IC50 data available in accessible scientific literature to provide a high-quality data set for further studies. Copyright © 2008 John Wiley & Sons, Ltd. [source]


Ethanol inhibits cold-menthol receptor TRPM8 by modulating its interaction with membrane phosphatidylinositol 4,5-bisphosphate

JOURNAL OF NEUROCHEMISTRY, Issue 1 2007
Jan Benedikt
Abstract Ethanol has opposite effects on two members of the transient receptor potential (TRP) family of ion channels: it inhibits the cold-menthol receptor TRPM8, whereas it potentiates the activity of the heat- and capsaicin-gated vanilloid receptor TRPV1. Both thermosensitive cation channels are critically regulated by the membrane lipid, phosphatidylinositol 4,5-bisphosphate (PIP2). The effects of this phospholipid on TRPM8 and TRPV1 are also functionally opposite: PIP2 is necessary for the activation of TRPM8 but it constitutively inhibits TRPV1. This parallel led us to investigate the possible role of PIP2 in the ethanol-induced modulation of rat TRPM8, heterologously expressed in HEK293T cells. In this study, we characterize the effects of ethanol (0.1,10%) on whole-cell currents produced by menthol and by low temperature (< 17°C). We show that the inclusion of PIP2 in the intracellular solution results in a strong reduction in the ethanol-induced inhibition of menthol-evoked responses. Conversely, intracellular dialysis with anti-PIP2 antibody or with the PIP2 scavenger, poly l -lysine, enhanced the ethanol-induced inhibition of TRPM8. A 20 min pre-incubation with wortmannin caused a modest decrease in inhibition produced by 1% ethanol, indicating that the ethanol-induced inhibition is not mediated by lipid kinases. These findings suggest that ethanol inhibits TRPM8 by weakening the PIP2,TRPM8 channel interaction; a similar mechanism may contribute to the ethanol-mediated modulation of some other PIP2 -sensitive TRP channels. [source]


SCM transmission in MM fiber with automatic selection of the subcarrier frequency

MICROWAVE AND OPTICAL TECHNOLOGY LETTERS, Issue 5 2009
Marcin Kowalczyk
Abstract Demonstrated was a 10 Mbit/s binary frequency shift keying subcarrier multiplexing system operating beyond the pass-band of 1 km MM graded index optical fiber. The system automatically adjusted the carrier frequency to the fiber frequency response. Transmission of four 10 Mbit/s channels was also shown over the same fiber. No visible channel interaction was observed. © 2009 Wiley Periodicals, Inc. Microwave Opt Technol Lett 51: 1212,1214, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.24277 [source]


Supply Chain Conflict Due to Store Brands: The Value of Wholesale Price Commitment in a Retail Supply Chain,

DECISION SCIENCES, Issue 2 2010
Ana Groznik
ABSTRACT Store brands are of increasing importance in retail supply chains, often causing channel conflict, as the retailer's product directly competes with the manufacturer's national brand. Extant research on the resulting channel interactions either assumes the national brand manufacturer can credibly commit to maintaining a wholesale price or that he lacks such ability. However, these two scenarios imply very different supply chain interactions, as only a national brand manufacturer with commitment ability can strategically adjust a national brand wholesale price to prevent a store brand introduction by the retailer. We specifically analyze the impact of this assumption on the manufacturer, the retailer, and the customers. We determine when long-term contracts that provide the manufacturer with such commitment ability can improve supply chain profitability. [source]


Calmodulin binding to M-type K+ channels assayed by TIRF/FRET in living cells

THE JOURNAL OF PHYSIOLOGY, Issue 9 2008
Manjot Bal
Calmodulin (CaM) binds to KCNQ2,4 channels within their carboxy termini, where it regulates channel function. The existing data have not resolved the Ca2+ dependence of the interaction between the channels and CaM. We performed glutathione S-transferase (GST)-pull-down assays between purified KCNQ2,4 carboxy termini and CaM proteins to determine the Ca2+ dependence of the interaction in vitro. The assays showed substantial Ca2+ dependence of the interaction of the channels with wild-type (WT) CaM, but not with dominant-negative (DN) CaM. To demonstrate CaM,channel interactions in individual living cells, we performed fluorescence resonance energy transfer (FRET) between ECFP-tagged KCNQ2,4 channels and EYFP-tagged CaM expressed in CHO cells, performed under total internal reflection fluorescence (TIRF) microscopy, in which excitation light only penetrates several hundred nanometres into the cell, thus isolating membrane events. FRET was assayed between the channels and either WT or DN CaM, performed under conditions of normal [Ca2+]i, low [Ca2+]i or high [Ca2+]i induced by empirically optimized bathing solutions. The FRET data suggest a strong Ca2+ dependence for the interaction between WT CaM and KCNQ2, but less so for KCNQ3 and KCNQ4. FRET between all KCNQ2,4 channels and DN CaM was robust, and not significantly Ca2+ dependent. These data show interactions between CaM and KCNQ channels in living cells, and suggest that the interactions between KCNQ2,4 channels and CaM are likely to have Ca2+ -dependent and Ca2+ -independent components. [source]