A5088999624- Ion channel regulation and function
- Ion Transport and Channel Regulation
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Electrolyte and hormonal disorders
- Magnesium in Health and Disease
- Connexins and lens biology
- Neuroscience and Neural Engineering
- Renal function and acid-base balance
- Neuroendocrine regulation and behavior
- Ion Channels and Receptors
- Hearing, Cochlea, Tinnitus, Genetics
- Adenosine and Purinergic Signaling
- Cystic Fibrosis Research Advances
- Cellular transport and secretion
- Barrier Structure and Function Studies
- Neuroscience of respiration and sleep
- Pancreatic function and diabetes
- Neonatal Respiratory Health Research
- Receptor Mechanisms and Signaling
- Photoreceptor and optogenetics research
- Calcium signaling and nucleotide metabolism
- Electrical and Bioimpedance Tomography
- Venomous Animal Envenomation and Studies
- Genetic Syndromes and Imprinting
Centre de Recherche des Cordeliers
2003-2019
Sorbonne Université
2009-2019
Université Paris Cité
2002-2019
Centre National de la Recherche Scientifique
2003-2019
Inserm
1999-2019
Metabolism and Renal Physiology
2011-2019
Sorbonne Paris Cité
2016-2019
Délégation Paris 5
2019
Centro de Estudios Científicos
2014
Centre National pour la Recherche Scientifique et Technique (CNRST)
2011
Bartter syndrome type 3 is a clinically heterogeneous hereditary salt-losing tubulopathy caused by mutations of the chloride voltage-gated channel Kb gene (CLCNKB), which encodes ClC-Kb involved in NaCl reabsorption renal tubule. To study phenotype/genotype correlations, we performed genetic analyses direct sequencing and multiplex ligation-dependent probe amplification retrospectively analyzed medical charts for 115 patients with CLCNKB mutations. Functional were Xenopus laevis oocytes...
Chloride transport by the renal tubule is critical for blood pressure (BP), acid-base, and potassium homeostasis. uptake from urinary fluid mediated various apical transporters, whereas basolateral chloride exit thought to be ClC-Ka/K1 ClC-Kb/K2, two channels ClC family, or KCl cotransporters SLC12 gene family. Nevertheless, localization role of ClC-K not fully resolved. Because inactivating mutations in ClC-Kb/K2 cause Bartter syndrome, a disease that mimics effects loop diuretic...
In this study, K + channels present in the basolateral membrane of distal convoluted tubule (DCT) were investigated using patch‐clamp methods. addition, Kir4.1, Kir4.2 and Kir5.1 inward rectifier RT‐PCR immunohistochemistry (Kir4.1). DCTs microdissected from collagenase‐treated mouse kidneys. One type channel was detected about 50 % cell‐attached patches DCT membrane; inwardly rectifying had an conductance ( g ) ∼40 pS at external [K ] 145 m . The current‐voltage relationship linear when...
K(+) channels in the basolateral membrane of mouse cortical collecting duct (CCD) principal cells were identified with patch-clamp technique, real-time PCR, and immunohistochemistry. In cell-attached patches, three conductances approximately 75, 40, 20 pS observed, but channel intermediate conductance (40 pS) predominated. inside-out patches exposed to an Mg(2+)-free medium, current-voltage relationship intermediate-conductance was linear a 38 pS. Addition 1.3 mM internal Mg(2+) had no...
The heteromeric inwardly rectifying Kir4.1/Kir5.1 K + channel underlies the basolateral conductance in distal nephron and is extremely sensitive to inhibition by intracellular pH. functional importance of renal ion transport has recently been highlighted mutations human Kir4.1 gene ( KCNJ10 ) that result seizures, sensorineural deafness, ataxia, mental retardation, electrolyte imbalance (SeSAME)/epilepsy, tubulopathy (EAST) syndrome, a complex disorder includes salt wasting hypokalemic...
Edema and ascites in nephrotic syndrome mainly result from increased Na<sup>+</sup> reabsorption along connecting tubules cortical collecting ducts (CCD). In puromycin aminonucleoside (PAN)-induced nephrosis, is associated with activity of the epithelial sodium channel (ENaC) Na<sup>+</sup>,K<sup>+</sup>-ATPase, two targets aldosterone. Because plasma aldosterone increases PAN-nephrotic rats, dependence ENaC activation PAN nephrosis was investigated. For this purpose, (<i>1</i>) mechanism...
The distal-convoluted tubule (DCT) of the kidney absorbs NaCl mainly via an Na+-Cl− cotransporter located at apical membrane, and Na+, K+ ATPase basolateral side. Cl− transport across membrane is thought to be conductive, but corresponding channels have not yet been characterized. In present study, we investigated on microdissected mouse DCTs using patch-clamp technique. A channel ∼9 pS was found in 50% cell-attached patches showing anionic selectivity. NPo modified when tubules were...
1. Chloride channels were identified in the basolateral membrane of isolated cortical thick ascending limbs (CTALs) mouse nephron by patch‐clamp technique. A channel with a conductance 45 pS, previously shown to be Cl‐ selective, was detected 21% cell‐attached patches when CTAL fragments pre‐incubated 10 mumol l‐4 forskolin for at least 15 min. The same found only 8.5% formed on unstimulated tubules. 2. Another smaller (7‐9 pS) 42.8% and 57% inside‐out tubules, but 82‐87% from...
Using the patch-clamp technique, we investigated Cl- channels on basolateral membrane of connecting tubule (CNT) and cortical collecting duct (CCD). We found a approximately 10-pS channel in CNT cell-attached patches. Substitution sodium gluconate for NaCl pipette shifted reversal potential by +25 mV, whereas N-methyl-D-gluconate chloride had no effect, indicating anion selectivity. On inside-out patches, determined selectivity sequence > Br- NO3(-) F-, which is compatible with that ClC-K2,...
This study investigates the presence and properties of Na+-activated K+ (KNa) channels in epithelial renal cells. Using real-time PCR on mouse microdissected nephron segments, we show that Slo2.2 mRNA, which encodes for KNa excitable cells, is expressed medullary cortical thick ascending limbs Henle's loop, but not other parts nephron. Patch-clamp analysis revealed a high conductance channel basolateral membrane both limbs. was highly selective (PK/PNa ∼ 20), its ranged from 140 to 180 pS...
1. Patch‐clamp single‐channel current recordings were used to study the inhibition of Ca2+‐activated non‐selective cation channels by internal nucleotides in patches excised from basolateral membranes thick ascending limb Henle's loop mouse kidney. 2. The application ATP, ADP or AMP cytoplasmic face inside‐out membrane reduced open‐state probability (Po) a dose‐dependent way without effect upon unitary amplitude. Dose‐response curves gave half‐maximal inhibitory concentrations 20, 21 and 2.5...
Pendrin, the chloride/bicarbonate exchanger of β-intercalated cells renal connecting tubule and collecting duct, plays a key role in NaCl reabsorption by distal nephron. Therefore, pendrin may be important for control extracellular fluid volume blood pressure.Here, we have used genetic mouse model which expression can switched-on vivo administration doxycycline. Pendrin also rapidly removed when doxycycline is discontinued. our strategy allows us to test selectively acute effects loss...
Mutations in the electrogenic Cl(-)/H(+) exchanger ClC-5 gene CLCN5 are frequently associated with Dent disease, an X-linked recessive disorder affecting proximal tubules. Here, we investigate consequences Xenopus laevis oocytes and HEK293 cells of nine previously reported, pathogenic, missense mutations ClC-5, most them which located regions forming subunit interface. Two mutants trafficked normally to cell surface early endosomes, displayed complex glycosylation at like wild-type but...
Mutations in the CLCNKB gene encoding ClC-Kb Cl(-) channel cause Bartter syndrome, which is a salt-losing renal tubulopathy. Here, we investigate functional consequences of seven mutations. When expressed Xenopus laevis oocytes, four mutants carried no current (c.736G>C, p.Gly246Arg; c.1271G>A, p.Gly424Glu; c.1313G>A, p.Arg438His; c.1316T>C, p.Leu439Pro), whereas others displayed 30%-60% reduction conductance as compared with wild-type (c.242T>C, p.Leu81Pro; c.274C>T, p.Arg92Trp; c.1052G>C,...
ClC-K2, a member of the ClC family Cl− channels and transporters, forms major basolateral conductance in distal nephron epithelial cells therefore plays central role renal absorption. However, its regulation remains largely unknown because fact that recombinant ClC-K2 has not yet been studied at single-channel level. In present study, we investigate effects voltage, pH, Cl−, Ca2+ on native membrane intercalated from mouse connecting tubule. The ∼10-pS channel shows steep voltage dependence...