scholarly journals Pharmacological Modulation of Ion Channels for the Treatment of Cystic Fibrosis

2021 ◽  
Vol Volume 13 ◽  
pp. 693-723
Author(s):  
Madalena C Pinto ◽  
Iris AL Silva ◽  
Miriam F Figueira ◽  
Margarida D Amaral ◽  
Miquéias Lopes-Pacheco
Keyword(s):  
Cystic Fibrosis ◽  
Ion Channels ◽  
Pharmacological Modulation

scholarly journals Small-molecule ion channels increase host defences in cystic fibrosis airway epithelia

Nature ◽  
2019 ◽  
Vol 567 (7748) ◽  
pp. 405-408 ◽  
Author(s):  
Katrina A. Muraglia ◽  
Rajeev S. Chorghade ◽  
Bo Ram Kim ◽  
Xiao Xiao Tang ◽  
Viral S. Shah ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Ion Channels ◽  
Small Molecule ◽  
Airway Epithelia ◽  
Cystic Fibrosis Airway

Pharmacological modulation of ion channels and transporters

Cell Calcium ◽  
2004 ◽  
Vol 35 (6) ◽  
pp. 575-582 ◽  
Author(s):  
Ursula Ravens ◽  
Erich Wettwer ◽  
Ottó Hála
Keyword(s):  
Ion Channels ◽  
Pharmacological Modulation

scholarly journals Regulation of ion channels in cystic fibrosis (869.8)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Katherine Henry ◽  
Eric Schiffhauer ◽  
Seakwoo Lee ◽  
Pamela Zeitlin
Keyword(s):  
Cystic Fibrosis ◽  
Ion Channels

Role of CFTR and Other Ion Channels in Cystic Fibrosis

2007 ◽  
pp. 23-41
Author(s):  
Karl Kunzelmann ◽  
Tanja Bachhuber ◽  
Gabriele Adam ◽  
Thilo Voelcker ◽  
Bettina Murle ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Ion Channels

scholarly journals Plasma membrane ion channels and epithelial to mesenchymal transition in cancer cells

2016 ◽  
Vol 23 (11) ◽  
pp. R517-R525 ◽  
Author(s):  
Iman Azimi ◽  
Gregory R Monteith
Keyword(s):  
Plasma Membrane ◽  
Ion Channels ◽  
Ion Channel ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Therapeutic Resistance ◽  
Therapeutic Approaches ◽  
Mesenchymal Transition ◽  
Pharmacological Modulation ◽  
Channel Expression

A variety of studies have suggested that epithelial to mesenchymal transition (EMT) may be important in the progression of cancer in patients through metastasis and/or therapeutic resistance. A number of pathways have been investigated in EMT in cancer cells. Recently, changes in plasma membrane ion channel expression as a consequence of EMT have been reported. Other studies have identified specific ion channels able to regulate aspects of EMT induction. The utility of plasma membrane ion channels as targets for pharmacological modulation make them attractive for therapeutic approaches to target EMT. In this review, we provide an overview of some of the key plasma membrane ion channel types and highlight some of the studies that are beginning to define changes in plasma membrane ion channels as a consequence of EMT and also their possible roles in EMT induction.

scholarly journals Ion channels as targets to treat cystic fibrosis lung disease

2018 ◽  
Vol 17 (2) ◽  
pp. S22-S27 ◽  
Author(s):  
S. Lorraine Martin ◽  
Vinciane Saint-Criq ◽  
Tzyh-Chang Hwang ◽  
László Csanády
Keyword(s):  
Cystic Fibrosis ◽  
Ion Channels ◽  
Lung Disease ◽  
Cystic Fibrosis Lung ◽  
Cystic Fibrosis Lung Disease

scholarly journals High-throughput characterization of 309 photocrosslinker-bearing ASIC1a variants maps residues critical for channel function and pharmacology

2020 ◽  
Author(s):  
Nina Braun ◽  
Søren Friis ◽  
Christian Ihling ◽  
Andrea Sinz ◽  
Jacob Andersen ◽  
...  
Keyword(s):  
Ion Channels ◽  
High Throughput ◽  
Mammalian Cells ◽  
Great Precision ◽  
Pharmacological Modulation ◽  
Current Decay ◽  
Human Acid ◽  
Automated Patch Clamp ◽  
Insight Into

AbstractIncorporation of non-canonical amino acids (ncAAs) can endow proteins with novel functionalities, such as crosslinking or fluorescence. In ion channels, the function of these variants can be studied with great precision using standard electrophysiology, but this approach is typically labor intensive and low throughput. Here, we establish a high-throughput protocol to conduct functional and pharmacological investigations of ncAA-containing hASIC1a (human acid-sensing ion channel 1a) variants in transiently transfected mammalian cells. We introduce three different photocrosslinking ncAAs into 103 positions and assess the function of the resulting 309 variants with automated patch-clamp (APC). We demonstrate that the approach is efficient and versatile, as it is amenable to assessing even complex pharmacological modulation by peptides. The data show that the acidic pocket is a major determinant for current decay and live-cell crosslinking provides insight into the hASIC1a-psalmotoxin-1 interaction. Overall, this protocol will enable future APC-based studies of ncAA-containing ion channels in mammalian cells.

Ion channels in normal human and cystic fibrosis sweat gland cells

1989 ◽  
Vol 257 (1) ◽  
pp. C129-C140 ◽  
Author(s):  
M. E. Krouse ◽  
G. Hagiwara ◽  
J. Chen ◽  
N. J. Lewiston ◽  
J. J. Wine
Keyword(s):  
Cystic Fibrosis ◽  
Ion Channels ◽  
Sweat Gland ◽  
Single Channel ◽  
Cell Types ◽  
Cation Channels ◽  
Secretory Cells ◽  
Anion Channels ◽  
Current Voltage ◽  
Normal Human

Single-channel patch-clamp techniques were used to study the population of apical membrane ion channels in cultured sweat gland secretory cells from normal and cystic fibrosis subjects. Four types of anion channels and two types of cation channels were found. At physiological voltages, anion channels had chord conductances of 10, 18, 24, and greater than 200 pS. All had linear current-voltage relations except the 24 pS channel, which showed outward rectification. Cation channels had chord conductances of 5 and 18 pS, were linear, and were nonselective for a variety of cations. Channel types and proportions were equivalent in control, cystic fibrosis, and cystic fibrosis heterozygote cells. Beyond showing that the distribution of channel types remains unchanged in cystic fibrosis cells, the data provide a basis for comparison with cells cultured under different conditions, with other cell types, and with native tissues.

scholarly journals Catalyst-like modulation of transition states for CFTR channel opening and closing: New stimulation strategy exploits nonequilibrium gating

2014 ◽  
Vol 143 (2) ◽  
pp. 269-287 ◽  
Author(s):  
László Csanády ◽  
Beáta Töröcsik
Keyword(s):  
Cystic Fibrosis ◽  
Ion Channels ◽  
Single Channel ◽  
Transition States ◽  
Chloride Ion ◽  
Open Probability ◽  
Gating Mechanism ◽  
Channel Opening ◽  
The Stability ◽  
Opening And Closing

Cystic fibrosis transmembrane conductance regulator (CFTR) is the chloride ion channel mutated in cystic fibrosis (CF) patients. It is an ATP-binding cassette protein, and its resulting cyclic nonequilibrium gating mechanism sets it apart from most other ion channels. The most common CF mutation (ΔF508) impairs folding of CFTR but also channel gating, reducing open probability (Po). This gating defect must be addressed to effectively treat CF. Combining single-channel and macroscopic current measurements in inside-out patches, we show here that the two effects of 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB) on CFTR, pore block and gating stimulation, are independent, suggesting action at distinct sites. Furthermore, detailed kinetic analysis revealed that NPPB potently increases Po, also of ΔF508 CFTR, by affecting the stability of gating transition states. This finding is unexpected, because for most ion channels, which gate at equilibrium, altering transition-state stabilities has no effect on Po; rather, agonists usually stimulate by stabilizing open states. Our results highlight how for CFTR, because of its unique cyclic mechanism, gating transition states determine Po and offer strategic targets for potentiator compounds to achieve maximal efficacy.

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