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A PDZ-interacting domain in CFTR is an apical membrane polarization signal.
TLDR
It is proposed that COOH-terminal deletions of CFTR result in defective vectorial chloride transport, partly by altering the polarized distribution ofCFTR in epithelial cells, and it is demonstrated that PDZ-interacting domains and PDZ domain-containing proteins play a key role in the apical polarization of ion channels in epithel cells. Expand
GCK-3, a Newly Identified Ste20 Kinase, Binds To and Regulates the Activity of a Cell Cycle–dependent ClC Anion Channel
TLDR
The studies provide new insight into physiologically relevant signaling pathways that control ClC channel activity and suggest novel mechanisms for coupling cell volume changes to cell cycle events and for coordinately regulating ion channels and transporters that control cellular Cl− content, cell volume, and epithelial fluid secretion. Expand
The PDZ-interacting domain of cystic fibrosis transmembrane conductance regulator is required for functional expression in the apical plasma membrane.
TLDR
It is concluded that the PDZ-interacting domain, in particular the leucine and threonine residues, are required for the efficient, polarized expression of CFTR in the apical plasma membrane, interaction with EBP50, and for the ability ofCFTR to mediate chloride secretion. Expand
ML297 (VU0456810), the first potent and selective activator of the GIRK potassium channel, displays antiepileptic properties in mice.
TLDR
The development and characterization of the first truly potent, effective, and selective GIRK activator, ML297, and it is demonstrated that ML297 is active in two in vivo models of epilepsy, a disease where up to 40% of patients remain with symptoms refractory to present treatments. Expand
Intracellular H+ regulates the α-subunit of ENaC, the epithelial Na+ channel.
TLDR
PHi but not pHo regulates ENaC and that the α-ENaC subunit is regulated directly by pHi, which is a first step to identifying the molecular mechanisms of proton-mediated regulation of apical membrane Na+ permeability in epithelia. Expand
Eliciting Renal Failure in Mosquitoes with a Small-Molecule Inhibitor of Inward-Rectifying Potassium Channels
TLDR
It is demonstrated that renal failure is a promising mechanism of action for killing mosquitoes, and the discovery of selective small-molecule inhibitors of mosquito Kir channels for use as insecticides is motivated. Expand
Localization and role of inward rectifier K(+) channels in Malpighian tubules of the yellow fever mosquito Aedes aegypti.
TLDR
An important role of AeKir1 and stellate cells in transepithelial K(+) transport under conditions of peritubular K(+ challenge is uncovered. Expand
G-protein independent coupling of the MC4R to Kir 7.1 in hypothalamic neurons
TLDR
It is shown that, in mice, regulation of firing activity of neurons from the paraventricular nucleus of the hypothalamus (PVN) by α-MSH and AgRP can be mediated independently of Gαs signalling by ligand-induced coupling of MC4R to closure of inwardly rectifying potassium channel, Kir7.1. Expand
Small-molecule modulators of inward rectifier K+ channels: recent advances and future possibilities.
TLDR
The purpose of this review is to provide a comprehensive summary of publicly disclosed Kir channel small-molecule modulators and highlight recent targeted drug-discovery efforts toward Kir1.1 and Kir2.1. Expand
Discovery and Characterization of a Potent and Selective Inhibitor of Aedes aegypti Inward Rectifier Potassium Channels
TLDR
Proof-of-concept that potent and highly selective inhibitors of mosquito Kir channels can be developed using conventional drug discovery approaches is demonstrated and reinforces the notion that the physical and chemical properties that determine a compound's bioavailability in vivo will be critical in determining the efficacy of Kir channel inhibitors as insecticides. Expand
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