The large size (six membrane-spanning repeats in each of four domains) and asymmetric architecture of the voltage-dependent Na+ channel has hindered determination of its structure. With the goal of determining the minimum structure of the Na+ channel permeation pathway, we created two stable cell lines expressing the voltage-dependent rat skeletal ... More
Sodium and chloride concentrations, pH, and depth of airway surface liquid in distal airways.
AuthorsSong Y, Thiagarajah J, Verkman AS
JournalJ Gen Physiol
PubMed ID14557401
The composition and depth of the airway surface liquid (ASL) are key parameters in airway physiology that are thought to be important in the pathophysiology of cystic fibrosis and other diseases of the airways. We reported novel fluorescent indicator and microscopy methods to measure [Na+], [Cl-], pH, and depth of ... More
Noninvasive in vivo fluorescence measurement of airway-surface liquid depth, salt concentration, and pH.
AuthorsJayaraman S, Song Y, Vetrivel L, Shankar L, Verkman AS
JournalJ Clin Invest
PubMed ID11160155
'The concentration of salt in the thin layer of fluid at the surface of large airways, the airway-surface liquid (ASL), is believed to be of central importance in airway physiology and in the pathophysiology of cystic fibrosis. Invasive sampling methods have yielded a wide range of ASL [NaCl] from 40 ... More
In vivo fluorescence measurement of Na(+) concentration in the pericryptal space of mouse descending colon.
AuthorsThiagarajah JR, Jayaraman S, Naftalin RJ, Verkman AS
JournalAm J Physiol Cell Physiol
PubMed ID11698248
'A method involving surgical exposure of the colonic mucosa, fluorescent dye addition, and confocal microscopy has been developed for monitoring colonic crypt function in vivo in mice. Na(+) concentration in the extracellular pericryptal space of descending colon was measured using a low-affinity Na(+)-sensitive fluorescent indicator consisting of an Na(+)-sensitive chromophore ... More
Cariporide (HOE642), a selective Na+-H+ exchange inhibitor, inhibits the mitochondrial death pathway.
AuthorsTeshima Y, Akao M, Jones SP, Marbán E
JournalCirculation
PubMed ID14568900
'BACKGROUND: The Na+-H+ exchanger figures prominently in cardiac ischemia-reperfusion injury. Several experimental and clinical studies have demonstrated a cardioprotective effect of Na+-H+ exchanger inhibition; however, the precise mechanisms have not been established. METHODS AND RESULTS: We examined the effects of cariporide (HOE642, 10 micromol/L) on cell death induced by oxidative ... More
Fluorescent sodium ion indicators based on the 1,7-diaza-15-crown-5 system.
AuthorsMartin VV, Rothe A, Diwu Z, Gee KR
JournalBioorg Med Chem Lett
PubMed ID15454218
A series of novel sodium ion-sensitive fluorescent reagents suitable for biological applications is described. The chelator nitrogen atom substituents affect the selectivity and affinity of cation binding, while the nature of the fluorophore determines the type of fluorescent response to metal ion chelation. ... More
A small molecule CFTR inhibitor produces cystic fibrosis-like submucosal gland fluid secretions in normal airways.
AuthorsThiagarajah JR, Song Y, Haggie PM, Verkman AS
JournalFASEB J
PubMed ID15001557
Airway submucosal glands have been proposed as a primary site for initiating and sustaining airway disease in cystic fibrosis (CF). However, it has been difficult to define the role of CFTR in gland fluid secretion because of concerns in interpreting experiments on diseased CF human airways subjected to chronic infection ... More
Submucosal gland secretions in airways from cystic fibrosis patients have normal [Na(+)] and pH but elevated viscosity.
AuthorsJayaraman S, Joo NS, Reitz B, Wine JJ, Verkman AS
JournalProc Natl Acad Sci U S A
PubMed ID11427704
Fluid and macromolecule secretion by submucosal glands in mammalian airways is believed to be important in normal airway physiology and in the pathophysiology of cystic fibrosis (CF). An in situ fluorescence method was applied to measure the ionic composition and viscosity of freshly secreted fluid from airway glands. Fragments of ... More
Role of mitochondrial Na+ concentration, measured by CoroNa red, in the protection of metabolically inhibited MDCK cells.
AuthorsBaron S, Caplanusi A, van de Ven M, Radu M, Despa S, Lambrichts I, Ameloot M, Steels P, Smets I
JournalJ Am Soc Nephrol
PubMed ID16221870
In ischemic or hypoxic tissues, elevated cytosolic calcium levels can induce lethal processes. Mitochondria, besides the endoplasmic reticulum, play a key role in clearing excessive cytosolic Ca2+. In a previous study, it was suggested that the clearance of cytosolic Ca2+, after approximately 18 min of metabolic inhibition (MI) in renal ... More
Effect of experimental dry eye on tear sodium concentration in the mouse.
AuthorsStewart P, Chen Z, Farley W, Olmos L, Pflugfelder SC
JournalEye Contact Lens
PubMed ID16021005
PURPOSE: To examine the changes in tear volume, sodium concentration, and osmolarity in BALB/c and C57BL/6J mice in response to experimental dry eye (EDE). METHODS: Tear volumes were determined at baseline and after 2 days of EDE using phenol red-impregnated cotton thread. Tear fluid was collected by instilling 1 microl ... More