A5049888042- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Electrolyte and hormonal disorders
- Renal and related cancers
- Genetic and Kidney Cyst Diseases
- Birth, Development, and Health
- Pediatric Urology and Nephrology Studies
- Renal function and acid-base balance
- Erythrocyte Function and Pathophysiology
- Biomedical Research and Pathophysiology
- Neonatal Health and Biochemistry
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Potassium and Related Disorders
- Neuroscience of respiration and sleep
- Nitric Oxide and Endothelin Effects
- Hormonal Regulation and Hypertension
- Dialysis and Renal Disease Management
- Genetic Syndromes and Imprinting
- Pancreatic function and diabetes
- Magnesium in Health and Disease
- Herpesvirus Infections and Treatments
- Chronic Kidney Disease and Diabetes
- Connexins and lens biology
- Liver Disease and Transplantation
Icahn School of Medicine at Mount Sinai
2015-2025
University of Nebraska Medical Center
2018
Vanderbilt University Medical Center
2018
Vanderbilt University
2018
Mount Sinai Medical Center
2009
The University of Texas Southwestern Medical Center
2008
New York Medical College
2008
University of Pittsburgh
2006
Belorusneft (Belarus)
2004
University of Pennsylvania
1999
Kidney Precision Medicine Project (KPMP) is building a spatially specified human kidney tissue atlas in health and disease with single-cell resolution. Here, we describe the construction of an integrated reference map cells, pathways, genes using unaffected regions nephrectomy tissues undiseased biopsies from 56 adult subjects. We use single-cell/nucleus transcriptomics, subsegmental laser microdissection transcriptomics proteomics, near-single-cell 3D CODEX imaging, spatial metabolomics to...
K+ secretion by the cortical collecting duct (CCD) is stimulated at high flow rates. Patch-clamp analysis has identified a small-conductance secretory (SK) and high-conductance Ca(2+)-activated (maxi-K) channel in apical membrane of CCD. The SK channel, encoded ROMK, believed to mediate baseline secretion. role stretch- Ca2+-activated maxi-K still uncertain. purpose this study was identify mediating flow-dependent Segments isolated from New Zealand White rabbits were microperfused absence...
An acute increase in tubular fluid flow rate the microperfused cortical collecting duct (CCD), associated with a ∼20% diameter, leads to an intracellular Ca 2+ concentration ([Ca ] i )in both principal and intercalated cells (Woda CB, Leite M Jr, Rohatgi R, Satlin LM. Am J Physiol Renal 283: F437-F446, 2002). The apical cilium present but not has been proposed be sensor. To determine whether across and/or epithelial stretch mediates [Ca response, CCDs from New Zealand White rabbits were...
Na + absorption in the renal cortical collecting duct (CCD) is mediated by apical epithelial channels (ENaCs). The CCD subject to continuous variations intraluminal flow rate that we speculate alters hydrostatic pressure, membrane stretch, and shear stress. Although ENaCs share limited sequence homology with putative mechanosensitive ion Caenorhabditis elegans,controversy exists as whether are regulated biomechanical forces. We examined effect of varying fluid on whole cell currents ( I )...
The proper function of the organs that make up urinary tract (kidneys, ureters, bladder, and urethra) depends on their ability to sense respond mechanical forces, including shear stress wall tension. However, we have limited understanding mechanosensors in these tissue sites which molecules are expressed. Possible candidates include stretch-activated PIEZO channels (PIEZO1 PIEZO2), been implicated mechanically regulated body functions touch sensation, proprioception, lung inflation, blood...
Ca2+-activated BK channels in renal intercalated cells (ICs) mediate luminal flow-induced K+ secretion (FIKS), but how ICs sense increased flow remains uncertain. We examined whether PIEZO1, a mechanosensitive Ca2+-permeable channel expressed the basolateral membranes of ICs, is required for FIKS. In isolated cortical collecting ducts (CCDs), cation-selective inhibitor GsMTx4 dampened increases intracellular Ca2+ concentration ([Ca2+]i), whereas PIEZO1 activator Yoda1 [Ca2+]i and activity....
Organic anion transporting polypeptide (oatp) is an integral membrane protein cloned from rat liver that mediates Na+-independent transport of organic anions such as sulfobromophthalein and taurocholic acid. Previous studies in hepatocytes suggested uptake associated with base exchange. To better characterize the mechanism oatp-mediated uptake, we examined taurocholate a HeLa cell line stably transfected oatp under regulation zinc-inducible promoter (Shi, X., Bai, S., Ford, A. C., Burk, R....
Autosomal recessive polycystic kidney disease (ARPKD) is characterized by the progressive dilatation of collecting ducts, nephron segments responsible for final renal regulation sodium, potassium, acid-base, and water balance. Murine models ARPKD possess mutations in genes encoding cilia-associated proteins, including Tg737 orpk mice. New findings implicate defects structure/function primary cilia as central to development disease. Our group (Liu W, Xu S, Woda C, Kim P, Weinbaum Satlin LM,...
The cellular pathways required for herpes simplex virus (HSV) invasion have not been defined. To test the hypothesis that HSV entry triggers activation of Ca2+-signaling pathways, effects on intracellular calcium concentration ([Ca2+]i) after exposure cells to were examined. Exposure results in a rapid and transient increase [Ca2+]i. Pretreatment with pharmacological agents block release inositol 1,4,5-triphosphate (IP3)-sensitive endoplasmic reticulum stores abrogates response. Moreover,...
Vectorial Na(+) absorption across the aldosterone-sensitive distal nephron plays a key role in regulation of extracellular fluid volume and blood pressure. Within this segment, diffuses from urinary into principal cells through an apical, amiloride-sensitive, epithelial channel (ENaC), which is considered to be rate-limiting step for absorption. We have reported that increases tubular flow rate microperfused rabbit cortical collecting ducts (CCDs) lead net laminar shear stress activate ENaC...
Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of PT uptake, we investigated processes in two distinct animal models. In a rat model acute exogenous overload, quantified sieving coefficients (GSC) uptake Texas Red-labeled serum using two-photon intravital microscopy. No change GSC was observed, but significant decrease quantified. second model,...
The cortical collecting duct (CCD) is a final site for regulation of K(+) homeostasis. CCD secretion determined by the electrochemical gradient and apical permeability to K(+). Conducting secretory (SK/ROMK) maxi-K channels are present in membrane CCD, former principal cells latter both intercalated cells. Whereas SK mediate baseline secretion, appear participate flow-stimulated secretion. Chronic dietary loading enhances capacity due, part, an increase channel density (Palmer et al., J Gen...
Nucleotide binding to purinergic P2 receptors contributes the regulation of a variety physiological functions in renal epithelial cells. Whereas have been functionally identified at basolateral membrane cortical collecting duct (CCD), final regulatory site urinary Na + , K and acid-base excretion, controversy exists as whether apical purinoceptors exist this segment. Nor has distribution receptor subtypes present on unique cell populations that constitute Ca 2+ CCD established. To examine...
Apical low-conductance SK and high-conductance Ca 2+ -activated BK channels are present in distal nephron, including the cortical collecting duct (CCD). Flow-stimulated net K secretion ( J ) CCD is 1) blocked by iberiotoxin, an inhibitor of but not channels, 2) associated with increase [Ca ] i , leading us to conclude that mediate flow-stimulated . To examine dependence sources contributing Na absorption were measured at slow (∼1) fast (∼5 nl·min −1 ·mm flow rates rabbit CCDs microperfused...
Renal epithelial cells release ATP constitutively under basal conditions and higher quantities of purine nucleotide in response to stimuli. filtered at the glomerulus, secreted by along nephron, released serosally macula densa for feedback signaling afferent arterioles within glomerulus has important physiological roles kidneys. In autosomal recessive polycystic kidney disease (ARPKD) mice humans, collecting duct lack an apical central cilium or express dysfunctional proteins that...
The renal outer medullary potassium (K<sup>+</sup>) channel, ROMK (Kir1.1), is a putative drug target for novel class of loop diuretic that would lower blood volume and pressure without causing hypokalemia. However, the lack selective inhibitors has hindered efforts to assess its therapeutic potential. In high-throughput screen small-molecule modulators ROMK, we previously identified potent moderately antagonist, 7,13-bis(4-nitrobenzyl)-1,4,10-trioxa-7,13-diazacyclopentadecane (VU590), also...
Fluid shear stress (FSS) is a critical regulator of cation transport in the collecting duct (CD). High-dietary sodium (Na) consumption increases urine flow, Na excretion, and prostaglandin E 2 (PGE ) excretion. We hypothesize that FSS elicited by increasing tubular flow rate induce release PGE from renal epithelial cells into extracellular compartment regulate ion transport. Media retrieved CD exposed to physiologic levels reveal several fold higher concentration compared with static...
The inward rectifier potassium (Kir) channel Kir4.1 (<i>KCNJ10</i>) carries out important physiologic roles in epithelial cells of the kidney, astrocytes central nervous system, and stria vascularis inner ear. Loss-of-function mutations <i>KCNJ10</i> lead to EAST/SeSAME syndrome, which is characterized by epilepsy, ataxia, renal salt wasting, sensorineural deafness. Although genetic approaches have been indispensable for establishing importance normal function these tissues, availability...
Key Points Bile acids activate the epithelial Na + channel (ENaC), which may lead to subsequent fluid retention in liver disease. duct ligation with spironolactone increased ENaC-dependent and without hormone-linked ENaC abundance. Counteracting bile acid activation be effective for treating Background Sodium disease is classically thought result from reduced circulating volume stimulation of renin-angiotensin-aldosterone system. However, evidence patients system suggests involvement...
Sex differences in renal tubular salt and water transporters, channels, claudins regulatory factors are evident all along the nephron. The influence of sex hormones on physiologic dimorphisms has been established studies removing, inhibiting or restoring their receptors. chromosome complement (SCC, XY vs. XX) transporter abundance activity is an open question. We employed Four Core Genotypes (FCG) mouse model (in which testis determining SRY gene deleted from Y inserted onto autosomal...
High urinary flow rates stimulate K secretion in the fully differentiated but not neonatal or weanling rabbit cortical collecting duct (CCD). Both small-conductance secretory and high-conductance Ca 2 + /stretch-activated maxi-K channels have been identified apical membrane of mature CCD by patch-clamp analysis. We reported that flow-stimulated net adult is 1) blocked TEA charybdotoxin, inhibitors intermediate- (maxi-K) -activated channels, 2) associated with increases Na absorption...
Net Na+ absorption in microperfused rabbit cortical collecting ducts (CCDs) is low during the 1st wk of postnatal life, increasing substantially thereafter [L. M. Satlin. Am. J. Physiol. 266 (Renal Fluid Electrolyte 35): F57-F65, 1994]. To establish whether rate observed immediately after birth due to a apical permeability neonatal principal cell, we used patch-clamp technique split-open CCDs isolated from maturing rabbits estimate conductance, number (N), and open probability (Po) channels...