Journal ArticleDOI
An Apical-Membrane Chloride Channel in Human Tracheal Epithelium
TLDR
Results suggest that an anion-selective channel that was not strongly voltage-gated or regulated by calcium in cell-free patches is responsible for the apical chloride conductance in airway epithelia.Abstract:
The mechanism of chloride transport by airway epithelia has been of substantial interest because airway and sweat gland-duct epithelia are chloride-impermeable in cystic fibrosis. The decreased chloride permeability prevents normal secretion by the airway epithelium, thereby interfering with mucociliary clearance and contributing to the morbidity and mortality of the disease. Because chloride secretion depends on and is regulated by chloride conductance in the apical cell membrane, the patch-clamp technique was used to directly examine single-channel currents in primary cultures of human tracheal epithelium. The cells contained an anion-selective channel that was not strongly voltage-gated or regulated by calcium in cell-free patches. The channel was also blocked by analogs of carboxylic acid that decrease apical chloride conductance in intact epithelia. When attached to the cell, the channel was activated by isoproterenol, although the channel was also observed to open spontaneously. However, in some cases, the channel was only observed after the patch was excised from the cell. These results suggest that this channel is responsible for the apical chloride conductance in airway epithelia.read more
Citations
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Journal ArticleDOI
Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.
John R. Riordan,Johanna M. Rommens,Batsheva Kerem,Noa Alon,Richard Rozmahel,Zbyszko Grzelczak,Julian Zielenski,Si Lok,Natasa Plavsic,Jia Ling Chou,Mitchell L. Drumm,Michael C. Iannuzzi,Francis S. Collins,Lap-Chee Tsui +13 more
TL;DR: A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients.
Journal ArticleDOI
Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis
Seng H. Cheng,Richard J. Gregory,John Marshall,Sucharita Paul,David W. Souza,Gary A. White,Catherine R. O'Riordan,Alan E. Smith +7 more
TL;DR: It is proposed that the mutant versions of CFTR are recognized as abnormal and remain incompletely processed in the endoplasmic reticulum where they are subsequently degraded.
Journal ArticleDOI
Effect of VX-770 in Persons with Cystic Fibrosis and the G551D-CFTR Mutation
Frank J. Accurso,Steven M. Rowe,John P. Clancy,Michael P. Boyle,Jordan M. Dunitz,Peter R. Durie,Scott D. Sagel,Douglas B. Hornick,Michael W. Konstan,Scott H. Donaldson,Richard B. Moss,Joseph M. Pilewski,Ronald C. Rubenstein,Ahmet Uluer,Moira L. Aitken,Steven D. Freedman,Lynn M. Rose,Nicole Mayer-Hamblett,Qunming Dong,Jiuhong Zha,Anne Stone,Eric R. Olson,Claudia L. Ordoñez,Preston W. Campbell,Melissa A. Ashlock,Bonnie W. Ramsey +25 more
TL;DR: This study showed that VX-770 was associated with within-subject improvements in CFTR and lung function and provides support for further studies of pharmacologic potentiation of CFTR as a means to treat cystic fibrosis.
Journal ArticleDOI
Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease
Karl Kunzelmann,Marcus A. Mall +1 more
TL;DR: Knowledge of the mechanisms of electrolyte transport in the colon enables the development of new strategies for the treatment of CF and secretory diarrhea and will lead to a better understanding of the pathophysiological events during inflammatory bowel disease and development of colonic carcinoma.
Book ChapterDOI
Membrane mechanisms and intracellular signalling in cell volume regulation.
TL;DR: The physiological significance of the regulation of cell volume and the role of amino acids, particularly taurine, as cellular osmolytes is discussed and possible mechanisms by which cells sense their volumes, along with the sensors of these signals, are discussed.
References
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Journal ArticleDOI
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
TL;DR: The extracellular patch clamp method, which first allowed the detection of single channel currents in biological membranes, has been further refined to enable higher current resolution, direct membrane patch potential control, and physical isolation of membrane patches.
Journal ArticleDOI
Chloride impermeability in cystic fibrosis.
Paul M. Quinton,Paul M. Quinton +1 more
TL;DR: Results are reported which suggest that abnormally low Cl− permeability in cystic fibrosis leads to poor reabsorption of NaCl in the sweat duct, and hence to a high concentration of Na Cl in theSweat duct.
Journal ArticleDOI
Abnormal ion permeation through cystic fibrosis respiratory epithelium
TL;DR: The increased voltage and amiloride efficacy in cystic fibrosis reflect absorption of sodium ions across an epithelium that is relatively impermeable to chloride ions.
Journal ArticleDOI
A candidate for the permeability pathway of the outer mitochondrial membrane
TL;DR: The extraction of channel-forming material from the outer membrane of rat liver mitochondria has properties which are essentially identical with those reported previously for voltage-dependent anion-selective channels (VDAC) from mitochondria of Paramecium.
Journal ArticleDOI
Single voltage-dependent chloride-selective channels of large conductance in cultured rat muscle
A. L. Blatz,Karl L. Magleby +1 more
TL;DR: Single-channel currents of an anion-selective channel in the plasma membrane of cultured rat muscle cells (myotubes) were recorded with the patch-clamp technique, and has an unusually large single-channel conductance of approximately 430 pS in symmetrical 143 mM KCl.