A5066682031- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Kidney Stones and Urolithiasis Treatments
- Pancreatic function and diabetes
- Renal and related cancers
- Renal function and acid-base balance
- Neuroscience and Neuropharmacology Research
- Membrane-based Ion Separation Techniques
- Nitric Oxide and Endothelin Effects
- Dialysis and Renal Disease Management
- Biomedical Research and Pathophysiology
- Cardiac electrophysiology and arrhythmias
- Connexins and lens biology
- Erythrocyte Function and Pathophysiology
- Neonatal Health and Biochemistry
- Electrolyte and hormonal disorders
- Amino Acid Enzymes and Metabolism
- Porphyrin Metabolism and Disorders
- Metabolism and Genetic Disorders
- Drug Transport and Resistance Mechanisms
- Pediatric Urology and Nephrology Studies
- Electrochemical Analysis and Applications
- Bipolar Disorder and Treatment
- Wnt/β-catenin signaling in development and cancer
- Magnesium in Health and Disease
Yale University
2014-2024
Friedrich-Alexander-Universität Erlangen-Nürnberg
2016
LMU Klinikum
2016
University of Cincinnati
2005
Harvard University
1986-2005
Beth Israel Deaconess Medical Center
2005
Howard Hughes Medical Institute
2004
Charité - Universitätsmedizin Berlin
2002
UConn Health
2002
University of Zurich
2002
We have examined the interaction of NH4+ and Li+ with Na+-H+ exchanger in rabbit renal microvillus membrane vesicles. Alkalinization intravesicular space, monitored [14C]DMO uptake by flow dialysis, resulted from addition Cl- salts Na+, Li+, or to external medium. The 22Na+ rate, assayed a rapid filtration technique, was saturable respect Na+ concentration (KT 6 mM Na+) competitively inhibited (Ki 1.9 mM) 4.3 mM). Efflux vesicles preloaded stimulated but Li+. conclude that has affinity for...
Regulation of sodium balance is a critical factor in the maintenance euvolemia, and dysregulation renal excretion results disorders altered intravascular volume, such as hypertension. The amiloride-sensitive epithelial channel (ENaC) thought to be only mechanism for transport cortical collecting duct (CCD) kidney. However, it has been found that much absorption CCD actually amiloride insensitive sensitive thiazide diuretics, which also block Na-Cl cotransporter (NCC) located distal...
Oxalate nephropathy with renal failure is caused by multiple disorders leading to hyperoxaluria due either overproduction of oxalate (primary hyperoxaluria) or excessive absorption dietary (enteric hyperoxaluria). To study the etiology in crystal-induced kidney disease, we created a model progressive feeding mice diet high soluble (high absence calcium). Renal histology was characterized intratubular calcium-oxalate crystal deposition an inflammatory response surrounding interstitium. not...
Na+/H+ exchangers in the brush-border (luminal, apical) membrane of renal proximal tubules are responsible for active, transcellular reabsorption NaHCO3 and NaCl. Although well characterized kinetically, protein that mediates exchange brush border has not been identified. Several exchanger genes, including NHE1, NHE2, NHE3, NHE4, expressed kidney. To identify NHE3 gene product to determine its cellular subcellular localization rabbit kidney, an NHE3-isoform-specific antibody was prepared....
The "housekeeping" sodium/hydrogen exchanger, NHE1, mediates the electroneutral 1:1 exchange of Na+ and H+ across plasma membrane. NHE1 is ubiquitous studied extensively for regulation pH i, cell volume, response to growth factors. We describe a spontaneous mouse mutant, s low-w ave e pilepsy, (swe), with neurological syndrome including ataxia unique epilepsy phenotype consisting 3/sec absence tonic-clonic seizures. swe was fine-mapped on Chromosome 4 identified as null allele Nhe1. Mutants...
A key function of the proximal tubule is retrieval most vast quantities NaCl and water filtered by kidney. Physiological studies using brush border vesicles perfused tubules have indicated that a major fraction Cl − reabsorption across apical membrane cells occurs via -formate exchange. The molecular identity transporter responsible for renal exchange has yet to be elucidated. As strategy identify one or more anion exchangers mediating in tubule, we screened expressed sequence tag database...
The Na+-dependent transport of D-glucose was studied in brush border membrane vesicles isolated from the rabbit renal cortex. presence a Na+ gradient between external incubation medium and intravesicular induced marked stimulation uptake. Accumulation sugar reached maximum then decreased, indicating efflux. final level uptake identical with that attained absence gradient, suggesting equilibrium established. At peak overshoot more than 10-fold value. These results suggest imposition large...
Recent studies suggest that the major pathway for exit of HC03-across basolateral membrane proximal tubule cell is electrogenic Na+/HC03-COtransport.We therefore evaluated possible presence Na+/HC03-co-transport in bawlatera1 vesicles isolated from rabbit renal cortex.Imposing an inward HC03-gradient induced transient uphill accumulation Na+, and imposing outward Na+ gradient caused HCO3"dependent generation inside-acid pH as monitored by quenching acridine orange fluorescence, findings...
We examined the effects of external H+ on kinetics Na+-H+ exchange in microvillus membrane vesicles isolated from rabbit renal cortex.The initial rate Na+ influx into with internal pH 6.0 was optimal at 8.5 and progressively inhibited as reduced to 6.0.A plot 1/V uersus [H+l0 linear yielded apparent K a = 35 n M (apparent pK 7.5).In studied 7.5 or 6.6, KN.was 13 54 mM, Kc for inhibition by Li+ 1.2 5.2 Ki NH,+ 11 50 Xi amiloride 7 25 pM, respectively.These findings were consistent competition...
Maintenance of extracellular K+ concentration within a narrow range is vital for numerous cell functions, particularly electrical excitability heart and muscle. Potassium homeostasis during intermittent ingestion involves rapid redistribution into the intracellular space to minimize increases in concentration, ultimate elimination load by renal excretion. Recent years have seen great progress identifying transporters channels involved extrarenal homeostasis. Here we apply these advances...
NHE3 is the predominant isoform responsible for apical membrane Na + /H exchange in proximal tubule. Deletion of by gene targeting results an −/− mouse with greatly reduced tubule[Formula: see text] absorption compared +/+ animals (P. J. Schultheis, L. Clarke, P. Meneton, M. Miller, Soleimani, R. Gawenis, T. Riddle, Duffy, Doetschman, Wang, G. Giebisch, S. Aronson, N. Lorenz, and E. Shull. Nature Genet. 19: 282–285, 1998). The purpose present study was to evaluate role other acidification...
We examined the effect of amiloride on Na+-H+ exchange in rabbit renal cortical microvillus membrane vesicles. Amiloride inhibited both uphill Na+ accumulation induced by imposition a transmembrane Hin+ greater than Hout+ gradient and H+ efflux Naout+ Nain+ gradient. The inhibitory influx was rapidly reversible fully competitive (Ki 3.0 X 10(-5) M amiloride, KT 6.3 mM Na+). In addition, from vesicles preloaded with Na+. However, diuretic did not inhibit such other Na+-coupled transport...
Although Na + /H exchanger isoform 3 (NHE3) mediates most exchange in the proximal tubule, studies of NHE3/NHE2 null mice suggest residual -dependent proton secretion (Choi JY, Shah M, Lee MG, Schultheis PJ, Shull GE, Muallem S, and Baum M. J Clin Invest 105: 1141–1146, 2000). To characterize additional NHE isoforms that might be expressed kidney, we identified partial sequence a novel NHE. PCR was used to define 5′- 3′-ends, cDNA encoding complete open reading frame amplified from mouse...
SLC26A6 (PAT1, CFEX) is an anion exchanger that expressed on the apical membrane of kidney proximal tubule and small intestine. Modes transport mediated by include Cl-/formate exchange, Cl-/HCO3- Cl-/oxalate exchange. To study its role in intestinal physiology, gene targeting was used to prepare mice lacking Slc26a6. Homozygous mutant Slc26a6-/- appeared healthy exhibited a normal blood pressure, function, plasma electrolyte profile. In tubules microperfused with low-HCO3-/high-Cl- solution,...
The major pathway for HCO3- transport across the basolateral membrane of proximal tubule cell is electrogenic Na+-HCO3- cotransport. In this study, we have determined stoichiometry cotransport system in vesicles that were isolated from rabbit renal cortex by Percoll gradient centrifugation. When potential approximated Nernst K+, as presence K+ ionophore valinomycin, equilibrium thermodynamics predicts should come to and mediate no net flux when (Na)i/(Na)o = [(HCO3)o/(HCO3)i]n[(K)o/(K)i]n-1,...
We have recently isolated cDNAs encoding a Na(+)-H+ exchanger isoform, referred to as NHE-1, from rabbit kidney and LLC-PK1 cells. To identify the NHE-1 protein establish its cellular subcellular localization in kidney, we prepared antibodies fusion protein. cDNA COOH-terminal 41 amino acids of was subcloned into maltose-binding vector purified (FP347A) used immunize guinea pigs. protein, performed Western blot analysis against membrane fractions renal cortex. Anti-FP347A antibody...