A5084777052- Magnesium in Health and Disease
- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Ion Channels and Receptors
- Parathyroid Disorders and Treatments
- Aluminum toxicity and tolerance in plants and animals
- Vitamin D Research Studies
- Electrolyte and hormonal disorders
- Plant Micronutrient Interactions and Effects
- Potassium and Related Disorders
- Cardiac electrophysiology and arrhythmias
- Trace Elements in Health
- Renal and related cancers
- Neuroscience and Neuropharmacology Research
- Pancreatic function and diabetes
- Hormonal Regulation and Hypertension
- Biomedical Research and Pathophysiology
- Erythrocyte Function and Pathophysiology
- Kidney Stones and Urolithiasis Treatments
- Genetic and Kidney Cyst Diseases
- Mitochondrial Function and Pathology
- Genetic Syndromes and Imprinting
- Connexins and lens biology
- Drug Transport and Resistance Mechanisms
- Neurobiology and Insect Physiology Research
Radboud University Nijmegen
2015-2024
Radboud University Medical Center
2015-2024
Radboud Institute for Molecular Life Sciences
2013-2022
University Medical Center
2013-2022
National Institutes of Health
2020
Yale University
2020
Harvard University
2020
Brigham and Women's Hospital
2020
Rockefeller University
2020
Federation of American Societies for Experimental Biology
2020
Vitamin D supplementation for the prevention of rickets is one oldest and most effective prophylactic measures in medicine, having virtually eradicated North America. Given potentially toxic effects vitamin D, recommendations optimal dose are still debated, part owing to increased incidence idiopathic infantile hypercalcemia Britain 1950s during a period high fortified milk products. We investigated molecular basis hypercalcemia, which characterized by severe failure thrive, vomiting,...
Mg2+ is an essential ion involved in a multitude of physiological and biochemical processes major constituent bone tissue. homeostasis mammals depends on the equilibrium between intestinal absorption renal excretion, but little known about molecular nature proteins transepithelial transport these organs. Recently, it was shown that patients with mutations TRPM6, member transient receptor potential family cation channels, suffer from hypomagnesemia secondary hypocalcemia (HSH) as result...
Blood calcium concentration is maintained within a narrow range despite large variations in dietary input and body demand. The Transient Receptor Potential ion channel TRPV5 has been implicated this process. We report here that stimulated by the mammalian hormone klotho. Klotho, β-glucuronidase, hydrolyzes extracellular sugar residues on TRPV5, entrapping plasma membrane. This maintains durable activity membrane permeability kidney. Thus, klotho activates cell surface hydrolysis of its...
In mammals, the extracellular calcium concentration is maintained within a narrow range despite large variations in daily dietary input and body demand. The small intestine kidney constitute influx pathways into Ca2+ pool and, therefore, play primary role homeostasis. We identified an apical Ca2+influx channel, which expressed proximal intestine, distal part of nephron placenta. This novel epithelial channel (ECaC) 730 amino acids contains six putative membrane-spanning domains with...
Rickets and hyperparathyroidism caused by a defective vitamin D receptor (VDR) can be prevented in humans animals high calcium intake, suggesting that intestinal absorption is critical for 1,25(OH) 2 [1,25(OH) 3 ] action on homeostasis. We assessed the rate of serum 45 Ca accumulation within 10 min oral gavage two strains VDR-knockout (KO) mice (Leuven Tokyo KO) observed 3-fold lower area under curve both KO strains. Moreover, we evaluated expression candidate genes involved transcellular...
ABSTRACT. The cyclic nucleotides cAMP and cGMP play key roles in cellular signaling the extracellular regulation of fluid balance. In kidney, is excreted across apical proximal tubular membrane into urine, where it reduces phosphate reabsorption through a dipyridamole-sensitive mechanism that not fully understood. It has long been known this efflux pathway dependent on ATP inhibited by probenecid. However, its identity whether shares same transporter have established. Here expression,...
Thiazide diuretics enhance renal Na+ excretion by blocking the Na+-Cl- cotransporter (NCC), and mutations in NCC result Gitelman syndrome. The mechanisms underlying accompanying hypocalciuria hypomagnesemia remain debated. Here, we show that enhanced passive Ca2+ transport proximal tubule rather than active distal convolution explains thiazide-induced hypocalciuria. First, micropuncture experiments mice demonstrated increased reabsorption of during chronic hydrochlorothiazide (HCTZ)...
Ca2+ ions play a fundamental role in many cellular processes, and the extracellular concentration of is kept under strict control to allow proper physiological functions take place. The kidney, small intestine, bone determine flux pool concerted fashion. Transient receptor potential (TRP) cation channel subfamily V, members 5 6 (TRPV5 TRPV6) have recently been postulated be molecular gatekeepers facilitating influx these tissues are TRP family, which mediates diverse biological effects...
Ca2+ ions play a fundamental role in many cellular processes, and the extracellular concentration of is kept under strict control to allow proper physiological functions take place. The kidney, small intestine, bone determine flux pool concerted fashion. Transient receptor potential (TRP) cation channel subfamily V, members 5 6 (TRPV5 TRPV6) have recently been postulated be molecular gatekeepers facilitating influx these tissues are TRP family, which mediates diverse biological effects...
Primary hypomagnesemia constitutes a rare heterogeneous group of disorders characterized by renal or intestinal magnesium (Mg2+) wasting resulting in generally shared symptoms Mg2+ depletion, such as tetany and generalized convulsions, often including associated disturbances calcium excretion. However, most the genes involved physiology handling are unknown. Through discovery mutation EGF gene isolated autosomal recessive hypomagnesemia, we have, for what believe is first time, identified...
Idiopathic infantile hypercalcemia (IIH) is characterized by severe with failure to thrive, vomiting, dehydration, and nephrocalcinosis. Recently, mutations in the vitamin D catabolizing enzyme 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1) were described that lead increased sensitivity due accumulation of active metabolite 1,25-(OH)2D3. In a subgroup patients who presented early infancy renal phosphate wasting symptomatic hypercalcemia, CYP24A1 excluded. Four from families parental...
Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common renal requiring replacement therapy (RRT). Still, there are few epidemiological data on prevalence of, and survival RRT for ADPKD. This study used from ERA-EDTA Registry in 12 European countries with 208 million inhabitants. We studied four 5-year periods (1991–2010). Survival analysis was performed by Kaplan–Meier method Cox proportional hazards regression. From first to last period, of ADPKD increased 56.8 91.1...
First published August 15, 2001; 10.1152/ajprenal. 00085.2001.—The organization of Na + and Ca 2+ transport pathways along the mouse distal nephron is incompletely known. We revealed by immunohistochemistry a set proteins convolution. The thiazide-sensitive -Cl − cotransporter (NCC) characterized convoluted tubule (DCT). amiloride-sensitive epithelial channel (ENaC) colocalized with NCC in late DCT (DCT2) extended to downstream connecting (CNT) collecting duct (CD). In early (DCT1),...
The recently cloned epithelial Ca<sup>2+</sup> channel (ECaC) constitutes the Ca<sup>2+</sup>influx pathway in 1,25-dihydroxyvitamin D<sub>3</sub>-responsive epithelia. We have combined patch-clamp analysis and fura-2 fluorescence microscopy to functionally characterize ECaC heterologously expressed HEK293 cells. intracellular concentration ECaC-expressing cells was closely correlated with applied electrochemical gradient, demonstrating distinctive permeability constitutive activation of...
Abstract. The recently cloned epithelial Ca 2+ channel (ECaC), which is expressed primarily in 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 )-responsive -transporting epithelia, postulated to constitute the rate-limiting step active reabsorption. In present study, effect of 1,25(OH) was investigated on ECaC mRNA and protein levels kidneys rats that were raised a vitamin D—depleting diet. This diet decreased serum concentration significantly, accompanied by marked drop level. Both normalized within...
The calcium release-activated channel (CRAC) is a highly Ca2+-selective ion that activated on depletion of inositol triphosphate (IP3)-sensitive intracellular Ca2+ stores. It was recently reported CaT1, member the TRP family cation channels, exhibits unique biophysical properties CRAC, which led to conclusion CaT1 comprises all or part CRAC pore (Yue, L., Peng, J. B., Hediger, M. A., and Clapham, D. E. (2001) Nature 410, 705–709). Here, we directly compare endogenous with heterologously...
1. The epithelial Ca(2+) channel (ECaC) family represents a unique group of Ca(2+)-selective channels that share limited homology to the ligand-gated capsaicin receptors, osmolarity-sensitive OTRPC4, as well transient receptor potential family. Southern blot analysis demonstrated this is restricted two members, ECaC1 and ECaC2 (also named CaT1). 2. RT-PCR are co-expressed in calbindin-D-containing epithelia, including small intestine, pancreas placenta, whereas kidney brain only express...
Abstract. The epithelial Ca 2+ channel (ECaC), which is exclusively expressed in 1,25-dihydroxyvitamin D 3 -responsive tissues, i.e. , kidney, intestine, and placenta, postulated to constitute the initial step process of transcellular transport. To strengthen this function, present study compares segmental cellular distribution ECaC other transport proteins known be involved In rabbit mRNA protein expression were primarily connecting tubule. Immunopositive staining for was found at apical...